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265 results on '"France Génomique"'

1. Predicting global distributions of eukaryotic plankton communities from satellite data

Author: Kyoto University, France Génomique, European Research Council, European Commission, Agencia Estatal de Investigación (España), Kaneko, Hiroto, Endo, Hisashi, Henry, Nicolas, Berney, Cédric, Mahé, Frédéric, Poulain, Julie, Labadie, Karine, Beluche, Odette, El Hourany, Roy, Tara Oceans Coordinators, Acinas, Silvia G., Chaffron, Samuel, Wincker, Patrick, Nakamura, Ryosuke, Karp-Boss, Lee, Boss, Emmanuel, Bowler, Chris, Vargas, Colomban de, Tomii, Kentaro, Ogata, Hiroyuki, Kyoto University, France Génomique, European Research Council, European Commission, Agencia Estatal de Investigación (España), Kaneko, Hiroto, Endo, Hisashi, Henry, Nicolas, Berney, Cédric, Mahé, Frédéric, Poulain, Julie, Labadie, Karine, Beluche, Odette, El Hourany, Roy, Tara Oceans Coordinators, Acinas, Silvia G., Chaffron, Samuel, Wincker, Patrick, Nakamura, Ryosuke, Karp-Boss, Lee, Boss, Emmanuel, Bowler, Chris, Vargas, Colomban de, Tomii, Kentaro, and Ogata, Hiroyuki
Abstract: Satellite remote sensing is a powerful tool to monitor the global dynamics of marine plankton. Previous research has focused on developing models to predict the size or taxonomic groups of phytoplankton. Here, we present an approach to identify community types from a global plankton network that includes phytoplankton and heterotrophic protists and to predict their biogeography using global satellite observations. Six plankton community types were identified from a co-occurrence network inferred using a novel rDNA 18 S V4 planetary-scale eukaryotic metabarcoding dataset. Machine learning techniques were then applied to construct a model that predicted these community types from satellite data. The model showed an overall 67% accuracy in the prediction of the community types. The prediction using 17 satellite-derived parameters showed better performance than that using only temperature and/or the concentration of chlorophyll a. The constructed model predicted the global spatiotemporal distribution of community types over 19 years. The predicted distributions exhibited strong seasonal changes in community types in the subarctic–subtropical boundary regions, which were consistent with previous field observations. The model also identified the long-term trends in the distribution of community types, which suggested responses to ocean warming
Published: 2023

2. Sex in the city: Uncovering sex-specific management of equine resources from prehistoric times to the Modern Period in France

Author: Centre National de la Recherche Scientifique (France), European Research Council, France Génomique, Université de Toulouse, Villum Fonden, Agence Nationale de la Recherche (France), Clavel, Benoît, Lepetz, Sébastien, Chauvey, Lorelei, Schiavinato, Stéphanie, Tonasso-Calvière, Laure, Liu, Xuexue, Fages, Antoine, Khan, Naveed, Seguin-Orlando, Andaine, Sarkissian, Clio Der, Clavel, Pierre, Estrada, Oscar, Alioğlu, Duha, Gaunitz, Charleen, Aury, Jean‐Marc, Barme, Maude, Bodu, Pierre, Olive, Monique, Binon-Lau, Olivier, Castel, Jean-Christophe, Boudadi-Maligne, Myriam, Boulbes, Nicolas, Bourgois, Alice, Decanter, Franck, Foucras, Sylvain, Frère, Stéphane, Gardeisen, Armelle, Jouanin, Gaëtan, Méla, Charlotte, Morant, Nicolas, Nieto-Espinet, Ariadna, Perdereau, Aude, Putelat, Olivier, Rivière, Julie, Robin, Opale, Salin, Marilyne, Valenzuela-Lamas, Silvia, Vallet, Christian, Yvinec, Jean-Hervé, Wincker, Patrick, Orlando, Ludovic, Centre National de la Recherche Scientifique (France), European Research Council, France Génomique, Université de Toulouse, Villum Fonden, Agence Nationale de la Recherche (France), Clavel, Benoît, Lepetz, Sébastien, Chauvey, Lorelei, Schiavinato, Stéphanie, Tonasso-Calvière, Laure, Liu, Xuexue, Fages, Antoine, Khan, Naveed, Seguin-Orlando, Andaine, Sarkissian, Clio Der, Clavel, Pierre, Estrada, Oscar, Alioğlu, Duha, Gaunitz, Charleen, Aury, Jean‐Marc, Barme, Maude, Bodu, Pierre, Olive, Monique, Binon-Lau, Olivier, Castel, Jean-Christophe, Boudadi-Maligne, Myriam, Boulbes, Nicolas, Bourgois, Alice, Decanter, Franck, Foucras, Sylvain, Frère, Stéphane, Gardeisen, Armelle, Jouanin, Gaëtan, Méla, Charlotte, Morant, Nicolas, Nieto-Espinet, Ariadna, Perdereau, Aude, Putelat, Olivier, Rivière, Julie, Robin, Opale, Salin, Marilyne, Valenzuela-Lamas, Silvia, Vallet, Christian, Yvinec, Jean-Hervé, Wincker, Patrick, and Orlando, Ludovic
Abstract: Sex identification from fragmentary archeozoological assemblages is particularly challenging in the Equid family, including for horses, donkeys and their hybrids. This limitation has precluded in-depth investigations of sex-ratio variation in various temporal, geographic and social contexts. Recently, shallow DNA sequencing has offered an economical solution to equine sex determination, even in environments where DNA preservation conditions is not optimal. In this study, we applied state-of-the-art methods in ancient DNA-based equine sex determination to 897 osseous remains in order to assess whether equal proportions of males and females could be found in a range of archeological contexts in France. We found Magdalenian horse hunt not focused on isolated bachelors, and Upper Paleolithic habitats and natural traps equally balancing sex ratios. In contrast, Iron Age sacrificial rituals appeared to have been preferentially oriented to male horses and this practice extended into the Roman Period. During Antiquity, the Middle Ages and the Modern Period, cities emerged as environments largely dominated by horse males. This strong sex-bias was considerably reduced, and sometimes even absent, in various rural contexts. Combined with previous archaeozoological work and textual evidence, our results portray an urban economy fueled by adult, often old, males, and rural environments where females and subadults of both sexes were maintained to sustain production demands.
Published: 2022

3. Parp3 promotes astrocytic differentiation through a tight regulation of Nox4-induced ROS and mTorc2 activation

Author: European Commission, Fundación Ramón Areces, Centre National de la Recherche Scientifique (France), Université de Strasbourg, France Génomique, Research Council of Norway, Norwegian Cancer Society, Rodriguez-Vargas, Martin-Hernandez, Kathline, Wang, Wei, Kunath, Nicolas, Suganthan, Rajikala, Amé,Jean-Christophe, Oliver, Francisco Javier, Ye, Jing, Bjørås, Magnar, Dantzer, Françoise, European Commission, Fundación Ramón Areces, Centre National de la Recherche Scientifique (France), Université de Strasbourg, France Génomique, Research Council of Norway, Norwegian Cancer Society, Rodriguez-Vargas, Martin-Hernandez, Kathline, Wang, Wei, Kunath, Nicolas, Suganthan, Rajikala, Amé,Jean-Christophe, Oliver, Francisco Javier, Ye, Jing, Bjørås, Magnar, and Dantzer, Françoise
Abstract: Parp3 is a member of the Poly(ADP-ribose) polymerase (Parp) family that has been characterized for its functions in strand break repair, chromosomal rearrangements, mitotic segregation and tumor aggressiveness. Yet its physiological implications remain unknown. Here we report a central function of Parp3 in the regulation of redox homeostasis in continuous neurogenesis in mice. We show that the absence of Parp3 provokes Nox4-induced oxidative stress and defective mTorc2 activation leading to inefficient differentiation of post-natal neural stem/progenitor cells to astrocytes. The accumulation of ROS contributes to the decreased activity of mTorc2 as a result of an oxidation-induced and Fbxw7-mediated ubiquitination and degradation of Rictor. In vivo, mTorc2 signaling is compromised in the striatum of naïve post-natal Parp3-deficient mice and 6 h after acute hypoxia-ischemia. These findings reveal a physiological function of Parp3 in the tight regulation of striatal oxidative stress and mTorc2 during astrocytic differentiation and in the acute phase of hypoxia-ischemia.
Published: 2020

4. Integrative visual omics of the white-rot fungus Polyporus brumalis exposes the biotechnological potential of its oxidative enzymes for delignifying raw plant biomass

Author: Alliance Nationale pour les Sciences de la Vie et de la Santé (France), European Molecular Biology Laboratory, Fondation ARC pour la Recherche sur le Cancer, France Génomique, GenoScreen, Grand Luminy Technopôle, Institut National de la Recherche Agronomique (France), Institut Paoli-Calmettes, omicX, Conseil Régional Provence-Alpes-Côte d'Azur, Département des Bouches-du-Rhône, Ville de Marseille, Drula, Elodie [0000-0002-9168-5214], Rancon, Anaïs [0000-0002-6258-0755], Henrissat, Bernard [0000-0002-3434-8588], Hainaut, Matthieu [0000-0002-7567-657X], Ruiz-Dueñas, F. J. [0000-0002-9837-5665], Herpoël-Gimbert, Isabelle [0000-0001-5518-8969], Navarro, David [0000-0002-3266-8270], Grigoriev, Igor V. [0000-0002-3136-8903], Raouche, Sana [0000-0001-5937-4902], Rosso, Marie-Noëlle https://orcid.org/0000-0001-8317-7220, Drula, Elodie, Miyauchi, Shingo, Rancon, Anaïs, Henrissat, Bernard, Hainaut, Matthieu, Ruiz-Dueñas, F. J., Herpoël-Gimbert, Isabelle, Navarro, David, Grigoriev, Igor V., Zhou, Simeng, Raouche, Sana, Rosso, Marie-Noëlle, Alliance Nationale pour les Sciences de la Vie et de la Santé (France), European Molecular Biology Laboratory, Fondation ARC pour la Recherche sur le Cancer, France Génomique, GenoScreen, Grand Luminy Technopôle, Institut National de la Recherche Agronomique (France), Institut Paoli-Calmettes, omicX, Conseil Régional Provence-Alpes-Côte d'Azur, Département des Bouches-du-Rhône, Ville de Marseille, Drula, Elodie [0000-0002-9168-5214], Rancon, Anaïs [0000-0002-6258-0755], Henrissat, Bernard [0000-0002-3434-8588], Hainaut, Matthieu [0000-0002-7567-657X], Ruiz-Dueñas, F. J. [0000-0002-9837-5665], Herpoël-Gimbert, Isabelle [0000-0001-5518-8969], Navarro, David [0000-0002-3266-8270], Grigoriev, Igor V. [0000-0002-3136-8903], Raouche, Sana [0000-0001-5937-4902], Rosso, Marie-Noëlle https://orcid.org/0000-0001-8317-7220, Drula, Elodie, Miyauchi, Shingo, Rancon, Anaïs, Henrissat, Bernard, Hainaut, Matthieu, Ruiz-Dueñas, F. J., Herpoël-Gimbert, Isabelle, Navarro, David, Grigoriev, Igor V., Zhou, Simeng, Raouche, Sana, and Rosso, Marie-Noëlle
Published: 2018

5. Accessing the genomic information of unculturable oceanic picoeukaryotes by combining multiple single cells

Author: Ministerio de Economía y Competitividad (España), Agence Nationale de la Recherche (France), National Science Foundation (US), European Commission, France Génomique, Mangot, Jean-François, Logares, Ramiro, Sánchez Fernández, Pablo, Latorre, Fran, Massana, Ramon, Ministerio de Economía y Competitividad (España), Agence Nationale de la Recherche (France), National Science Foundation (US), European Commission, France Génomique, Mangot, Jean-François, Logares, Ramiro, Sánchez Fernández, Pablo, Latorre, Fran, and Massana, Ramon
Abstract: Pico-sized eukaryotes play key roles in the functioning of marine ecosystems, but we still have a limited knowledge on their ecology and evolution. The MAST-4 lineage is of particular interest, since it is widespread in surface oceans, presents ecotypic differentiation and has defied culturing efforts so far. Single cell genomics (SCG) are promising tools to retrieve genomic information from these uncultured organisms. However, SCG are based on whole genome amplification, which normally introduces amplification biases that limit the amount of genomic data retrieved from a single cell. Here, we increase the recovery of genomic information from two MAST-4 lineages by co-assembling short reads from multiple Single Amplified Genomes (SAGs) belonging to evolutionary closely related cells. We found that complementary genomic information is retrieved from different SAGs, generating co-assembly that features >74% of genome recovery, against about 20% when assembled individually. Even though this approach is not aimed at generating high-quality draft genomes, it allows accessing to the genomic information of microbes that would otherwise remain unreachable. Since most of the picoeukaryotes still remain uncultured, our work serves as a proof-of-concept that can be applied to other taxa in order to extract genomic data and address new ecological and evolutionary questions
Published: 2017

6. Generation of coherent spin-wave modes in yttrium iron garnet microdiscs by spin–orbit torque

Author: France Génomique, Direction Générale de l'Armement (France), Région Auvergne-Rhône-Alpes, Russian Government, Kazan Federal University, Collet, Martin, Milly, X. de, Kelly, O. d’Allivy, Naletov, V. V., Bernard, R., Bortolotti, Paolo, Ben Youssef, J., Demidov, V. E., Demokritov, S.O., Prieto, J. L., Muñoz Sánchez, Manuel, Cros, Vicent, Anane, Abdelmadjid, Loubens, G. de, Klein, Oliver, France Génomique, Direction Générale de l'Armement (France), Région Auvergne-Rhône-Alpes, Russian Government, Kazan Federal University, Collet, Martin, Milly, X. de, Kelly, O. d’Allivy, Naletov, V. V., Bernard, R., Bortolotti, Paolo, Ben Youssef, J., Demidov, V. E., Demokritov, S.O., Prieto, J. L., Muñoz Sánchez, Manuel, Cros, Vicent, Anane, Abdelmadjid, Loubens, G. de, and Klein, Oliver
Abstract: In recent years, spin–orbit effects have been widely used to produce and detect spin currents in spintronic devices. The peculiar symmetry of the spin Hall effect allows creation of a spin accumulation at the interface between a metal with strong spin–orbit interaction and a magnetic insulator, which can lead to a net pure spin current flowing from the metal into the insulator. This spin current applies a torque on the magnetization, which can eventually be driven into steady motion. Tailoring this experiment on extended films has proven to be elusive, probably due to mode competition. This requires the reduction of both the thickness and lateral size to reach full damping compensation. Here we show clear evidence of coherent spin–orbit torque-induced auto-oscillation in micron-sized yttrium iron garnet discs of thickness 20 nm. Our results emphasize the key role of quasi-degenerate spin-wave modes, which increase the threshold current.
Published: 2016

7. Delineating ecologically significant taxonomic units from global patterns of marine picocyanobacteria

Author: European Commission, Natural Environment Research Council (UK), France Génomique, Agence Nationale de la Recherche (France), Farrant, Gregory K., Cornejo-Castillo, Francisco M., Acinas, Silvia G., Garczarek, Laurence, European Commission, Natural Environment Research Council (UK), France Génomique, Agence Nationale de la Recherche (France), Farrant, Gregory K., Cornejo-Castillo, Francisco M., Acinas, Silvia G., and Garczarek, Laurence
Abstract: Prochlorococcus and Synechococcus are the two most abundant and widespread phytoplankton in the global ocean. To better understand the factors controlling their biogeography, a reference database of the high-resolution taxonomic marker petB, encoding cytochrome b6, was used to recruit reads out of 109 metagenomes from the Tara Oceans expedition. An unsuspected novel genetic diversity was unveiled within both genera, even for the most abundant and well-characterized clades, and 136 divergent petB sequences were successfully assembled from metagenomic reads, significantly enriching the reference database. We then defined Ecologically Significant Taxonomic Units (ESTUs)—that is, organisms belonging to the same clade and occupying a common oceanic niche. Three major ESTU assemblages were identified along the cruise transect for Prochlorococcus and eight for Synechococcus. Although Prochlorococcus HLIIIA and HLIVA ESTUs codominated in iron-depleted areas of the Pacific Ocean, CRD1 and the yet-to-be cultured EnvB were the prevalent Synechococcus clades in this area, with three different CRD1 and EnvB ESTUs occupying distinct ecological niches with regard to iron availability and temperature. Sharp community shifts were also observed over short geographic distances—for example, around the Marquesas Islands or between southern Indian and Atlantic Oceans—pointing to a tight correlation between ESTU assemblages and specific physico-chemical parameters. Together, this study demonstrates that there is a previously overlooked, ecologically meaningful, fine-scale diversity within some currently defined picocyanobacterial ecotypes, bringing novel insights into the ecology, diversity, and biology of the two most abundant phototrophs on Earth
Published: 2016

8. Cyanobacterial symbionts diverged in the late Cretaceous towards lineage-specific nitrogen fixation factories in single-celled phytoplankton

Author: European Molecular Biology Laboratory, Agence Nationale de la Recherche (France), France Génomique, Consejo Superior de Investigaciones Científicas (España), Ministerio de Ciencia e Innovación (España), Cornejo-Castillo, Francisco M., Cabello, Ana María, Salazar, Guillem, Gasol, Josep M., Massana, Ramon, Acinas, Silvia G., European Molecular Biology Laboratory, Agence Nationale de la Recherche (France), France Génomique, Consejo Superior de Investigaciones Científicas (España), Ministerio de Ciencia e Innovación (España), Cornejo-Castillo, Francisco M., Cabello, Ana María, Salazar, Guillem, Gasol, Josep M., Massana, Ramon, and Acinas, Silvia G.
Abstract: The unicellular cyanobacterium UCYN-A, one of the major contributors to nitrogen fixation in the open ocean, lives in symbiosis with single-celled phytoplankton. UCYN-A includes several closely related lineages whose partner fidelity, genome-wide expression and time of evolutionary divergence remain to be resolved. Here we detect and distinguish UCYN-A1 and UCYN-A2 lineages in symbiosis with two distinct prymnesiophyte partners in the South Atlantic Ocean. Both symbiotic systems are lineage specific and differ in the number of UCYN-A cells involved. Our analyses infer a streamlined genome expression towards nitrogen fixation in both UCYN-A lineages. Comparative genomics reveal a strong purifying selection in UCYN-A1 and UCYN-A2 with a diversification process ~91 Myr ago, in the late Cretaceous, after the low-nutrient regime period occurred during the Jurassic. These findings suggest that UCYN-A diversified in a co-evolutionary process, wherein their prymnesiophyte partners acted as a barrier driving an allopatric speciation of extant UCYN-A lineages
Published: 2016

9. A chromosome-level, haplotype-phased Vanilla planifolia genome highlights the challenge of partial endoreplication for accurate whole-genome assembly

Author: Piet, Quentin, Droc, Gaetan, Marande, William, Sarah, Gautier, Bocs, Stéphanie, Klopp, Christophe, Bourge, Mickael, Siljak-Yakovlev, Sonja, Bouchez, Olivier, Lopez-Roques, Céline, Lepers-Andrzejewski, Sandra, Bourgois, Laurent, Zucca, Joseph, Dron, Michel, Besse, Pascale, Grisoni, Michel, Jourda, Cyril, Charron, Carine, Peuplements végétaux et bioagresseurs en milieu tropical (UMR PVBMT), Centre de Coopération Internationale en Recherche Agronomique pour le Développement (Cirad)-Institut de Recherche pour le Développement (IRD)-Université de La Réunion (UR)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Amélioration génétique et adaptation des plantes méditerranéennes et tropicales (UMR AGAP), Centre de Coopération Internationale en Recherche Agronomique pour le Développement (Cirad)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Institut Agro Montpellier, Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Université de Montpellier (UM), Département Systèmes Biologiques (Cirad-BIOS), Centre de Coopération Internationale en Recherche Agronomique pour le Développement (Cirad), South Green Bioinformatics Platform [Montpellier], Centre National de Ressources Génomiques Végétales (CNRGV), Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Plateforme Bio-Informatique - Génotoul, Génopole Toulouse Midi-Pyrénées [Auzeville] (GENOTOUL), Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Ecole Nationale Vétérinaire de Toulouse (ENVT), Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Unité de Mathématiques et Informatique Appliquées de Toulouse (MIAT INRAE), Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-BioInfOmics, Unité de Mathématiques et Informatique Appliquées de Toulouse (MIAT INRAE), Institut de Biologie Intégrative de la Cellule (I2BC), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS), Ecologie Systématique et Evolution (ESE), AgroParisTech-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS), Génome et Transcriptome - Plateforme Génomique ( GeT-PlaGe), Plateforme Génome & Transcriptome (GET), Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Génopole Toulouse Midi-Pyrénées [Auzeville] (GENOTOUL), Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Etablissement public Vanille de Tahiti, Eurovanille, V. Mane Fils, 620 route de Grasse, 06620 Le Bar sur Loup, France., Institut des Sciences des Plantes de Paris-Saclay (IPS2 (UMR_9213 / UMR_1403)), Université d'Évry-Val-d'Essonne (UEVE)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), This work was supported by grants from Eurovanille and V. Mane Fils companies. The research was co-funded by the Centre de Coopération Internationale en Recherche Agronomique pour le Développement (CIRAD), the Université de La Réunion (UR), the Institut National de Recherche pour l’Agriculture l’Alimentation et l’Environnement (INRAE), the Centre National de la Recherche Scientifique (CNRS), and the Etablissement Vanille de Tahiti (EVT). This work was also supported by grants from the European Regional Development Fund (ERDF), the Conseil Régional de la Réunion, and the Conseil Départemental de la Réunion. This work was supported by France Génomique National infrastructure, funded as part of 'Investissement d’avenir' program managed by Agence Nationale pour la Recherche (ANR-10-INBS-0009, France Génomique) and has also benefited from Imagerie-Gif core facility, supported by l’Agence Nationale de la Recherche (ANR-11-EQPX-0029 Morphoscope 2, ANR-10-INBS-04 France BioImaging, ANR-11-IDEX-0003-02 IDEX Paris-Saclay)., ANR-10-INBS-0009,France-Génomique,Organisation et montée en puissance d'une Infrastructure Nationale de Génomique(2010), ANR-11-EQPX-0029,MORPHOSCOPE 2,Imagerie et reconstruction multiéchelles de la morphogenèse. (Plateforme d'innovation technologique et méthodologique pour l'imagerie in vivo et la reconstruction des dynamiques multiéchelles de la morphogenèse)(2011), ANR-10-INBS-0004,France-BioImaging,Développment d'une infrastructure française distribuée coordonnée(2010), and ANR-11-IDEX-0003,IPS,Idex Paris-Saclay(2011)
Subjects: optical mapping, Genome Size, Haplotypes, partial endoreplication, vanilla, whole-genome sequencing, [SDV]Life Sciences [q-bio], genome hub, Endoreduplication, Chromosomes
Abstract: International audience; Vanilla planifolia, the species cultivated to produce one of the world’s most popular flavors, is highly prone to partial genome endoreplication, which leads to highly unbalanced DNA content in cells. We report here the first molecular evidence of partial endoreplication at the chromosome scale by the assembly and annotation of an accurate haplotype-phased genome of V. planifolia. Cytogenetic data demonstrated that the diploid genome size is 4.09 Gb, with 16 chromosome pairs, although aneuploid cells are frequently observed. Using PacBio HiFi and optical mapping, we assembled and phased a diploid genome of 3.4 Gb with a scaffold N50 of 1.2 Mb and 59 128 predicted protein-coding genes. The atypical k-mer frequencies and the uneven sequencing depth observed agreed with our expectation of unbalanced genome representation. Sixty-seven percent of the genes were scattered over only 30% of the genome, putatively linking gene-rich regions and the endoreplication phenomenon. By contrast, low-coverage regions (non-endoreplicated) were rich in repeated elements but also contained 33% of the annotated genes. Furthermore, this assembly showed distinct haplotype-specific sequencing depth variation patterns, suggesting complex molecular regulation of endoreplication along the chromosomes. This high-quality, anchored assembly represents 83% of the estimated V. planifolia genome. It provides a significant step toward the elucidation of this complex genome. To support post-genomics efforts, we developed the Vanilla Genome Hub, a user-friendly integrated web portal that enables centralized access to high-throughput genomic and other omics data and interoperable use of bioinformatics tools.
Published: 2022
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10. Genome-wide mapping of individual replication fork velocities using nanopore sequencing

Author: Bertrand Theulot, Laurent Lacroix, Jean-Michel Arbona, Gael A. Millot, Etienne Jean, Corinne Cruaud, Jade Pellet, Florence Proux, Magali Hennion, Stefan Engelen, Arnaud Lemainque, Benjamin Audit, Olivier Hyrien, Benoît Le Tallec, Institut de biologie de l'ENS Paris (IBENS), Département de Biologie - ENS Paris, École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Laboratoire de biologie et modélisation de la cellule (LBMC UMR 5239), École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut Pasteur [Paris], Genoscope - Centre national de séquençage [Evry] (GENOSCOPE), Université Paris-Saclay-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Centre épigénétique et destin cellulaire (EDC (UMR_7216)), Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPC), Université Paris Cité (UPC), Centre National de la Recherche Scientifique (CNRS), Laboratoire de Physique de l'ENS Lyon (Phys-ENS), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), This work was supported by the Ligue Nationale Contre le Cancer, the Association pour la Recherche sur le Cancer, the Agence Nationale de la Recherche [ANR-18-CE45-0002 to B.A. and ANR-19-CE12-0028 toO.H.], the Fondation pour la Recherche Médicale [FRM DEI201512344404 to O.H.] and the Cancéropôle Ile-de-France [PLBIO16-302 to O.H.]. This work was partly supported by the Genoscope, the Commissariat à l’Energie Atomique et aux Energies Alternatives (CEA) and France Génomique [ANR-10-INBS-09-08]. B.T. was supported by fellowships from the Ministère de l’Enseignement Supérieur et de la Recherche and the Fondation pour la Recherche Médicale [FRM FDT202106013030]., millot, gael, APPEL À PROJETS GÉNÉRIQUE 2018 - Le sequençage nanopore pour une cartographie haute-performance de la réplication de l'ADN - - NanoPoRep2018 - ANR-18-CE45-0002 - AAPG2018 - VALID, Origines de réplication humaines : réconcilier des visions disparates - - HUDROR2019 - ANR-19-CE12-0028 - AAPG2019 - VALID, Organisation et montée en puissance d'une Infrastructure Nationale de Génomique - - France-Génomique2010 - ANR-10-INBS-0009 - INBS - VALID, Collège Doctoral, Sorbonne Université (SU), Hub Bioinformatique et Biostatistique - Bioinformatics and Biostatistics HUB, Institut Pasteur [Paris] (IP)-Université Paris Cité (UPCité), Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Génomique métabolique (UMR 8030), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université d'Évry-Val-d'Essonne (UEVE)-Centre National de la Recherche Scientifique (CNRS), This work was supported by the Ligue Nationale Contre le Cancer, the Association pour la Recherche sur le Cancer, the Agence Nationale de la Recherche [ANR-18-CE45-0002 to B.A. and ANR-19-CE12-0028 to O.H.], the Fondation pour la Recherche Médicale [FRM DEI201512344404 to O.H.] and the Cancéropôle Ile-de-France [PLBIO16-302 to O.H.]. This work was partly supported by the Genoscope, the Commissariat à l’Energie Atomique et aux Energies Alternatives (CEA) and France Génomique [ANR-10-INBS-09-08]. B.T. was supported by fellowships from the Ministère de l’Enseignement Supérieur et de la Recherche and the Fondation pour la Recherche Médicale [FRM FDT202106013030]., ANR-18-CE45-0002,NanoPoRep,Le sequençage nanopore pour une cartographie haute-performance de la réplication de l'ADN(2018), ANR-19-CE12-0028,HUDROR,Origines de réplication humaines : réconcilier des visions disparates(2019), ANR-10-INBS-0009,France-Génomique,Organisation et montée en puissance d'une Infrastructure Nationale de Génomique(2010), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Centre épigénétique et destin cellulaire (EDC), and École normale supérieure de Lyon (ENS de Lyon)-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)
Subjects: [SDV] Life Sciences [q-bio], DNA Replication, Nanopore Sequencing, Multidisciplinary, Bromodeoxyuridine, [SDV]Life Sciences [q-bio], [SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], General Physics and Astronomy, General Chemistry, Saccharomyces cerevisiae, General Biochemistry, Genetics and Molecular Biology, Chromosomes
Abstract: Little is known about replication fork velocity variations along eukaryotic genomes, since reference techniques to determine fork speed either provide no sequence information or suffer from low throughput. Here we present NanoForkSpeed, a nanopore sequencing-based method to map and extract the velocity of individual forks detected as tracks of the thymidine analogue bromodeoxyuridine incorporated during a brief pulse-labelling of asynchronously growing cells. NanoForkSpeed retrieves previous Saccharomyces cerevisiae mean fork speed estimates (≈2 kb/min) in the BT1 strain exhibiting highly efficient bromodeoxyuridine incorporation and wild-type growth, and precisely quantifies speed changes in cells with altered replisome progression or exposed to hydroxyurea. The positioning of >125,000 fork velocities provides a genome-wide map of fork progression based on individual fork rates, showing a uniform fork speed across yeast chromosomes except for a marked slowdown at known pausing sites.
Published: 2022
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11. The population structure of Clostridium tetani deduced from its pan-genome

Author: Laure Diancourt, Laurence Ma, Michel R. Popoff, Lucile Plourde, Christiane Bouchier, Diana Chapeton-Montes, Alexis Criscuolo, Holger Brüggemann, Toxines bactériennes - Bacterial Toxins, Institut Pasteur [Paris] (IP), Sanofi Pasteur [Marcy-l'Étoile, France], Génomique (Plate-Forme) - Genomics Platform, Centre National de Référence des Bactéries Anaérobies et Botulisme - National Reference Center Anaerobic Bacteria and Botulism (CNR), Hub Bioinformatique et Biostatistique - Bioinformatics and Biostatistics HUB, Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Aarhus University [Aarhus], This work was supported by Sanofi-Pasteur and Institut Pasteur., We thank C. Fund, France Génomique, for technical assistance, and we thank Genomics Platform (PF1), member of 'France Génomique' consortium (ANR10-INBS-09-08), for high throughput sequencing., Institut Pasteur [Paris], and Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS)
Subjects: 0301 basic medicine, Clostridium tetani, PROTEINS, BOTULINUM NEUROTOXIN, [SDV]Life Sciences [q-bio], Population, lcsh:Medicine, Virulence, [SDV.BC]Life Sciences [q-bio]/Cellular Biology, [SDV.BC.BC]Life Sciences [q-bio]/Cellular Biology/Subcellular Processes [q-bio.SC], Biology, medicine.disease_cause, SEQUENCE, Genome, Article, ZINC, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Plasmid, [SDV.BC.IC]Life Sciences [q-bio]/Cellular Biology/Cell Behavior [q-bio.CB], medicine, Genetics, NEUROTRANSMITTER RELEASE, BACTERIAL TOXINS, lcsh:Science, education, Tetanolysin, education.field_of_study, Multidisciplinary, IDENTIFICATION, Phylogenetic tree, STRAINS, lcsh:R, Pan-genome, Bacteriology, musculoskeletal system, GENE, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, 3. Good health, 030104 developmental biology, [SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology, chemistry, lcsh:Q, 030217 neurology & neurosurgery
Abstract: Clostridium tetani produces a potent neurotoxin, the tetanus neurotoxin (TeNT) that is responsible for the worldwide neurological disease tetanus, but which can be efficiently prevented by vaccination with tetanus toxoid. Until now only one type of TeNT has been characterized and very little information exists about the heterogeneity among C. tetani strains. We report here the genome sequences of 26 C. tetani strains, isolated between 1949 and 2017 and obtained from different locations. Genome analyses revealed that the C. tetani population is distributed in two phylogenetic clades, a major and a minor one, with no evidence for clade separation based on geographical origin or time of isolation. The chromosome of C. tetani is highly conserved; in contrast, the TeNT-encoding plasmid shows substantial heterogeneity. TeNT itself is highly conserved among all strains; the most relevant difference is an insertion of four amino acids in the C-terminal receptor-binding domain in four strains that might impact on receptor-binding properties. Other putative virulence factors, including tetanolysin and collagenase, are encoded in all genomes. This study highlights the population structure of C. tetani and suggests that tetanus-causing strains did not undergo extensive evolutionary diversification, as judged from the high conservation of its main virulence factors.
Published: 2019
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12. Identification of the master sex determining gene in Northern pike (Esox lucius) reveals restricted sex chromosome differentiation

Author: Amaury Herpin, Ming Wen, Jean-Paul Concordet, Julien Bobe, Jean-Mickael Busnel, René Guyomard, Estelle Vigouroux, Ayaka Yano, Jérôme Lluch, Laurent Journot, Elodie Jouanno, Romain Feron, Manfred Schartl, Yann Guiguen, Christophe Klopp, Qiaowei Pan, Hugues Parrinello, John H. Postlethwait, Céline Roques, Laboratoire de Physiologie et Génomique des Poissons (LPGP), Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique )-Institut National de la Recherche Agronomique (INRA), Department of Ecology and Evolution [Lausanne], Université de Lausanne (UNIL), Génétique Animale et Biologie Intégrative (GABI), AgroParisTech-Institut National de la Recherche Agronomique (INRA), Fédération d'Ille-et-Vilaine pour la pêche et la protection du milieu aquatique [Rennes] (FDPPMA 35), Structure et Instabilité des Génomes (STRING), Muséum national d'Histoire naturelle (MNHN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Chimie du CNRS (INC)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Institut de Génomique Fonctionnelle (IGF), Université de Montpellier (UM)-Université Montpellier 1 (UM1)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Montpellier 2 - Sciences et Techniques (UM2)-Centre National de la Recherche Scientifique (CNRS), Plateforme Bio-Informatique - Génotoul, Institut National de la Recherche Agronomique (INRA), Système d'Information des GENomes des Animaux d'Elevage (SIGENAE), Génétique Physiologie et Systèmes d'Elevage (GenPhySE ), École nationale supérieure agronomique de Toulouse [ENSAT]-Institut National de la Recherche Agronomique (INRA)-Ecole Nationale Vétérinaire de Toulouse (ENVT), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées, Génome et Transcriptome - Plateforme Génomique (GeT-PlaGe), Institut National de la Recherche Agronomique (INRA)-Plateforme Génome & Transcriptome (GET), Génopole Toulouse Midi-Pyrénées [Auzeville] (GENOTOUL), Institut National des Sciences Appliquées - Toulouse (INSA Toulouse), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Ecole Nationale Vétérinaire de Toulouse (ENVT), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Institut National des Sciences Appliquées - Toulouse (INSA Toulouse), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Génopole Toulouse Midi-Pyrénées [Auzeville] (GENOTOUL), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Institute of Neuroscience [Eugene, OR, États-Unis], University of Oregon [Eugene], Department of Physiological Chemistry [Würzburg, Allemagne], University of Würzburg-Biocenter [Würzburg, Allemagne], Comprehensive Cancer Center Mainfranken [Würzburg, Allemagne], University Hospital of Würzburg, Department of Biology [College Station, TX, États-Unis], Hagler Institute for Advanced Study [College Station, TX, États-Unis], Texas A&M University [College Station]-Texas A&M University [College Station], This project was supported by funds from the 'Agence Nationale de la Recherche' and the 'Deutsche Forschungsgemeinschaft' (ANR/DFG, PhyloSex project, 2014-2016) to YG and MS. The GeT core facility (JL, CR), Toulouse, France and the MGX facility, Montpellier, France (LJ, HP) were supported by France Génomique National infrastructure, funded as part of 'Investissement d’avenir' program managed by Agence Nationale pour la Recherche (contract ANR-10-INBS-09)., ANR-13-ISV7-0005,PhyloSex,Evolution des déterminants majeurs du sexe chez les poissons.(2013), ANR-10-INBS-0009,France-Génomique,Organisation et montée en puissance d'une Infrastructure Nationale de Génomique(2010), Institut National de la Recherche Agronomique (INRA)-AgroParisTech, Institut National de la Recherche Agronomique (INRA)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Department of Ecology and Evolution, Sorbonne Université (SU), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Unité de Mathématiques et Informatique Appliquées de Toulouse (MIAT INRA), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Toulouse III - Paul Sabatier (UT3), Institute of Neuroscience, Physiological Chemistry, Biocenter, Julius-Maximilians-Universität Würzburg [Wurtzbourg, Allemagne] (JMU), Comprehensive Cancer Center Mainfranken, University Clinic Würzburg, Hagler Institute for Advanced Study and Department of Biology, Texas A&M University System, This project was supported by funds from the 'Agence Nationale de la Recherche' and the 'Deutsche Forschungsgemeinschaft' (ANR/ DFG, PhyloSex project, 2014-2016) to YG and MS. The GeT core facility (JL, CR), Toulouse, France and the MGX facility, Montpellier, France (LJ, HP) were supported by France Génomique National infrastructure, funded as part of 'Investissement d’avenir' program managed by Agence Nationale pour la Recherche (contract ANR-10-INBS-09), Bodescot, Myriam, Blanc – Accords bilatéraux 2013 - Evolution des déterminants majeurs du sexe chez les poissons. - - PhyloSex2013 - ANR-13-ISV7-0005 - Blanc – Accords bilatéraux 2013 - VALID, Organisation et montée en puissance d'une Infrastructure Nationale de Génomique - - France-Génomique2010 - ANR-10-INBS-0009 - INBS - VALID, Université de Lausanne = University of Lausanne (UNIL), Institut National de la Recherche Agronomique (INRA)-Ecole Nationale Vétérinaire de Toulouse (ENVT), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-École nationale supérieure agronomique de Toulouse [ENSAT], Dpt of Ecology and Evolution [Lausanne], Muséum national d'Histoire naturelle (MNHN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), BioCampus Montpellier (BCM), Université Montpellier 1 (UM1)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Plateforme Bioinformatique Genotoul [Castanet-Tolosan], Institut National de la Recherche Agronomique (INRA)-Institut National de la Recherche Agronomique (INRA), GeT PlaGe, Genotoul, ANR-10-INBS-09-01/10-INBS-0009,France-Génomique,Organisation et montée en puissance d'une Infrastructure Nationale de Génomique(2010), Julius-Maximilians-Universität Würzburg (JMU), and ProdInra, Migration
Subjects: Anti-Mullerian Hormone, Male, Evolution of sexual reproduction, [SDV]Life Sciences [q-bio], gène déterminant majeur du sexe, [MATH] Mathematics [math], [SDV.GEN] Life Sciences [q-bio]/Genetics, QH426-470, Animals, Genetically Modified, mâle, Database and Informatics Methods, 0302 clinical medicine, duplication de gènes, poisson, Gene Duplication, Gene duplication, Morphogenesis, Medicine and Health Sciences, chromosome sexuel, [MATH]Mathematics [math], Phylogeny, Genetics, détermination du sexe, 0303 health sciences, education.field_of_study, Sex Chromosomes, Sexual Differentiation, Chromosome Biology, Chromosome Mapping, Animals, Anti-Mullerian Hormone/genetics, Esocidae/physiology, Female, Gene Knockdown Techniques, Sex Chromosomes/genetics, Sex Determination Processes/genetics, Synteny, Genomics, [SDV] Life Sciences [q-bio], séquençage du génome, hormone antimullérienne, [SDV.BBM.GTP] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], Anatomy, Sequence Analysis, Genital Anatomy, différenciation sexuelle, expression des gènes, Research Article, Bioinformatics, Population, Locus (genetics), [SDV.GEN.GA] Life Sciences [q-bio]/Genetics/Animal genetics, [INFO] Computer Science [cs], Biology, Research and Analysis Methods, DNA sequencing, Chromosomes, reproduction, 03 medical and health sciences, esox lucius, [SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], [INFO]Computer Science [cs], education, Molecular Biology Techniques, Gonads, Gene, Molecular Biology, 030304 developmental biology, Whole genome sequencing, [SDV.GEN]Life Sciences [q-bio]/Genetics, Sequence Assembly Tools, génome, Gene Mapping, Reproductive System, Chromosome, Biology and Life Sciences, Computational Biology, Cell Biology, Sex Determination, Sex Determination Processes, Genome Analysis, [SDV.GEN.GA]Life Sciences [q-bio]/Genetics/Animal genetics, Genetic Loci, Esocidae, Sequence Alignment, 030217 neurology & neurosurgery, Developmental Biology
Abstract: Teleost fishes, thanks to their rapid evolution of sex determination mechanisms, provide remarkable opportunities to study the formation of sex chromosomes and the mechanisms driving the birth of new master sex determining (MSD) genes. However, the evolutionary interplay between the sex chromosomes and the MSD genes they harbor is rather unexplored. We characterized a male-specific duplicate of the anti-Müllerian hormone (amh) as the MSD gene in Northern Pike (Esox lucius), using genomic and expression evidence as well as by loss-of-function and gain-of-function experiments. Using RAD-Sequencing from a family panel, we identified Linkage Group (LG) 24 as the sex chromosome and positioned the sex locus in its sub-telomeric region. Furthermore, we demonstrated that this MSD originated from an ancient duplication of the autosomal amh gene, which was subsequently translocated to LG24. Using sex-specific pooled genome sequencing and a new male genome sequence assembled using Nanopore long reads, we also characterized the differentiation of the X and Y chromosomes, revealing a small male-specific insertion containing the MSD gene and a limited region with reduced recombination. Our study reveals an unexpectedly low level of differentiation between a pair of sex chromosomes harboring an old MSD gene in a wild teleost fish population, and highlights both the pivotal role of genes from the amh pathway in sex determination, as well as the importance of gene duplication as a mechanism driving the turnover of sex chromosomes in this clade., Author summary In stark contrast to mammals and birds, a high proportion of teleosts have homomorphic sex chromosomes and display a high diversity of sex determining genes. Yet, population level knowledge of both the sex chromosome and the master sex determining gene is only available for the Japanese medaka, a model species. Here we identified and provided functional proofs of an old duplicate of anti-Müllerian hormone (Amh), a member of the Tgf- β family, as the male master sex determining gene in the Northern pike, Esox lucius. We found that this duplicate, named amhby (Y-chromosome-specific anti-Müllerian hormone paralog b), was translocated to the sub-telomeric region of the new sex chromosome, and now amhby shows strong sequence divergence as well as substantial expression pattern differences from its autosomal paralog, amha. We assembled a male genome sequence using Nanopore long reads and identified a restricted region of differentiation within the sex chromosome pair in a wild population. Our results provide insight on the conserved players in sex determination pathways, the mechanisms of sex chromosome turnover, and the diversity of levels of differentiation between homomorphic sex chromosomes in teleosts.
Published: 2019
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13. Genome sequence of the euryhaline Javafish medaka, Oryzias javanicus: a small aquarium fish model for studies on adaptation to salinity

Author: Amaury Herpin, Manfred Schartl, Shigeki Yasumasu, Cédric Cabau, Koji Inoue, Margot Zahm, Kiyoshi Naruse, Céline Roques, Célia Barrachina, Cécile Donnadieu, Yusuke Takehana, Christophe Klopp, Yann Guiguen, Mari Kawaguchi, Chuya Shinzato, Olivier Bouchez, Laurent Journot, Satoshi Ansai, Nagahama Institute of Bio-Science and Technology, Unité de Mathématiques et Informatique Appliquées de Toulouse (MIAT INRA), Institut National de la Recherche Agronomique (INRA), Génétique Physiologie et Systèmes d'Elevage (GenPhySE ), Institut National de la Recherche Agronomique (INRA)-Ecole Nationale Vétérinaire de Toulouse (ENVT), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-École nationale supérieure agronomique de Toulouse [ENSAT], Génome et Transcriptome - Plateforme Génomique (GeT-PlaGe), Institut National de la Recherche Agronomique (INRA)-Plateforme Génome & Transcriptome (GET), Génopole Toulouse Midi-Pyrénées [Auzeville] (GENOTOUL), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Ecole Nationale Vétérinaire de Toulouse (ENVT), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Génopole Toulouse Midi-Pyrénées [Auzeville] (GENOTOUL), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Institut de Génomique Fonctionnelle - Montpellier GenomiX (IGF MGX), Institut de Génomique Fonctionnelle (IGF), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-BioCampus (BCM), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Sophia University, Laboratory of Bioresources, National Institute for Basic Biology [Okazaki], Atmosphere and Ocean Research Institute [Kashiwa-shi] (AORI), The University of Tokyo (UTokyo), Developmental Biochemistry, Biocenter, Julius-Maximilians-Universität Würzburg (JMU), Comprehensive Cancer Center Mainfranken, University Hospital, Hagler Institute for Advanced Study and Department of Biology, Texas A&M University System, Laboratoire de Physiologie et Génomique des Poissons (LPGP), Institut National de la Recherche Agronomique (INRA)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Hunan Normal University (HNU), This work was supported by a 'Projet Incitatif PHASE department 2015' grant (Grant ID ACI_PHASE, Institut National de la Recherche Agronomique) to AH, a NIBB Collaborative Research Initiative to KN, NIBB individual Collaboration Research Project to MK, and Grants-in-Aid for Young Scientists to YT (Grant ID 16K18590) and MK (Grant ID 16K18593). The GeT and MGX core facilities were supported by France Génomique National infrastructure, funded as partof 'Investissement d’avenir' program managed by Agence Nationale pour la Recherche (contract ANR-10-INBS-09). The GeT core facility was also supported by the 409 GET-PACBIO program (« Programme operationnel FEDER-FSE MIDI-PYRENEES ET GARONNE 2014-2020 »), ANR-10-INBS-0009,France-Génomique,Organisation et montée en puissance d'une Infrastructure Nationale de Génomique(2010), ANR-16-COFA-0004,AquaCrispr,Optimization of the CRISPR/Cas9 knock-in technology and application in salmon and trout(2016), ProdInra, Migration, Organisation et montée en puissance d'une Infrastructure Nationale de Génomique - - France-Génomique2010 - ANR-10-INBS-0009 - INBS - VALID, Optimization of the CRISPR/Cas9 knock-in technology and application in salmon and trout - - AquaCrispr2016 - ANR-16-COFA-0004 - COFA - VALID, Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Ecole Nationale Vétérinaire de Toulouse (ENVT), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-École nationale supérieure agronomique de Toulouse [ENSAT]-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Génome et Transcriptome - Plateforme Génomique, Université de Montpellier (UM)-Université Montpellier 1 (UM1)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Montpellier 2 - Sciences et Techniques (UM2)-Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM)-Université Montpellier 1 (UM1)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Montpellier 2 - Sciences et Techniques (UM2)-Centre National de la Recherche Scientifique (CNRS), The University of Tokyo, Julius-Maximilians-Universität Würzburg [Wurtzbourg, Allemagne] (JMU), Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Hunan Normal University, This work was supported by a 'Projet Incitatif PHASE department 2015' grant (Grant ID ACI_PHASE, INRAE) to AH, a NIBB Collaborative Research Initiative to KN, NIBB individual Collaboration Research Project to MK, and Grants-in-Aid for Young Scientists to YT (Grant ID 16K18590) and MK (Grant ID 16K18593). AH was additionally funded by the project AquaCRISPR (ANR-16-COFA-0004-01). The GeT and MGX core facilities were supported by France Génomique National infrastructure, funded as part of 'Investissement d’avenir' program managed by Agence Nationale pour la Recherche (contract ANR-10-INBS-09). The GeT core facility was also supported by the GET-PACBIO program (« Programme opérationnel FEDER-FSE Midi-Pyrénées et Garonne 2014-2020 »), ANR-10- INBS0009,INBS,France-Génomique, Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique )-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Institut National des Sciences Appliquées - Toulouse (INSA Toulouse), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Institut National des Sciences Appliquées - Toulouse (INSA Toulouse), This work was supported by a 'Projet Incitatif PHASE department 2015' grant (Grant ID ACI_PHASE, INRAE) to AH, a NIBB Collaborative Research Initiative to KN, NIBB individual Collaboration Research Project to MK, and Grants-in-Aid for Young Scientists to YT (Grant ID 16K18590) and MK (Grant ID 16K18593). AH was additionally funded by the project AquaCRISPR (ANR-16-COFA-0004-01). The GeT and MGX core facilities were supported by France Génomique National infrastructure, funded as part of 'Investissement d’avenir' program managed by Agence Nationale pour la Recherche (contract ANR-10-INBS-09). The GeT core facility was also supported by the GET-PACBIO program (« Programme operationnel FEDER-FSE MIDI-PYRENEES ET GARONNE 2014-2020 »), École nationale supérieure agronomique de Toulouse [ENSAT]-Institut National de la Recherche Agronomique (INRA)-Ecole Nationale Vétérinaire de Toulouse (ENVT), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées, Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique )-Institut National de la Recherche Agronomique (INRA), Centre National de la Recherche Scientifique (CNRS)-Université Montpellier 2 - Sciences et Techniques (UM2)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Montpellier 1 (UM1)-Centre National de la Recherche Scientifique (CNRS)-Université Montpellier 2 - Sciences et Techniques (UM2)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Montpellier 1 (UM1), and Unité de Mathématiques et Informatique Appliquées de Toulouse (MIAT INRAE)
Subjects: 0106 biological sciences, Salinity, carte génétique, Evolution, [SDV]Life Sciences [q-bio], séquençage du génome complet, Sequence assembly, [SDV.GEN] Life Sciences [q-bio]/Genetics, [SDV.GEN.GA] Life Sciences [q-bio]/Genetics/Animal genetics, QH426-470, Long reads, [INFO] Computer Science [cs], 010603 evolutionary biology, 01 natural sciences, Genome, identification de gènes, adaptation comportementale, 03 medical and health sciences, Genetic map, Genome editing, poisson, Genetics, [INFO]Computer Science [cs], 14. Life underwater, adrianichthyidae, Adaptation, 030304 developmental biology, Whole genome sequencing, tolérance à la salinité, 0303 health sciences, whole genome sequencing, Whole genome sequencing WGS, [SDV.GEN]Life Sciences [q-bio]/Genetics, Phylogenetic tree, biology, Euryhaline, biology.organism_classification, Medaka, osmorégulation, [SDV] Life Sciences [q-bio], [SDV.GEN.GA]Life Sciences [q-bio]/Genetics/Animal genetics, espèce modèle, séquençage du génome, eau de mer, Evolutionary biology, Oryzias javanicus, Transcriptome
Abstract: BackgroundThe genus Oryzias is constituted of 35 medaka-fish species each exhibiting various ecological, morphological and physiological peculiarities and adaptations. Beyond of being a comprehensive phylogenetic group for studying intra-genus evolution of several traits like sex determination, behaviour, morphology or adaptation through comparative genomic approaches, all medaka species share many advantages of experimental model organisms including small size and short generation time, transparent embryos and genome editing tools for reverse and forward genetic studies. The Java medaka, Oryzias javanicus, is one of the two species of medaka perfectly adapted for living in brackish/sea-waters. Being an important component of the mangrove ecosystem, O. javanicus is also used as a valuable marine test-fish for ecotoxicology studies. Here, we sequenced and assembled the whole genome of O. javanicus, and anticipate this resource will be catalytic for a wide range of comparative genomic, phylogenetic and functional studies.FindingsComplementary sequencing approaches including long-read technology and data integration with a genetic map allowed the final assembly of 908 Mbp of the O. javanicus genome. Further analyses estimate that the O. javanicus genome contains 33% of repeat sequences and has a heterozygosity of 0.96%. The achieved draft assembly contains 525 scaffolds with a total length of 809.7 Mbp, a N50 of 6.3 Mbp and a L50 of 37 scaffolds. We identified 21454 expressed transcripts for a total transcriptome size of 57, 146, 583 bps.ConclusionsWe provide here a high-quality draft genome assembly of the euryhaline Javafish medaka, and give emphasis on the evolutionary adaptation to salinity.
Published: 2019
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14. Generating genomic platforms to studyCandida albicanspathogenesis

Author: Corinne Maufrais, Sadri Znaidi, Irena Maslanka, Charlotte Majgier, Renaud A. Julien, Carol A. Munro, Louise A. Walker, Laurence Arbogast, Sophie Bachellier-Bassi, Yogesh Chaudhari, Ute Zeidler, Laurence Ma, Keunsook K. Lee, Murielle Chauvel, Tristan Rossignol, Floris Schoeters, Christophe d'Enfert, Christiane Bouchier, Audrey Nesseir, Emmanuelle Permal, Hélène Tournu, Magali Tichit, Vitor Cabral, Mélanie Legrand, Patrick Van Dijck, Helene Boyer, Biologie et Pathogénicité fongiques, Institut Pasteur [Paris]-Institut National de la Recherche Agronomique (INRA), University of Aberdeen, Catholic University of Leuven - Katholieke Universiteit Leuven (KU Leuven), Hub Bioinformatique et Biostatistique - Bioinformatics and Biostatistics HUB, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Modul-Bio, Biomics, Centre de Recherche et Innovation Technologique (CITECH), Institut Pasteur [Paris]-Institut Pasteur [Paris], Wellcome Trust [088858/Z/09/Z to C.A.M., C.D.], European Commission (FINSysB) [PITN-GA-2008-214004 to C.D.] Agence Nationale de la Recherche [KANJI, ANR-08-MIE-033-01 to C.D., CANDICOL, ANR-10-01 to C.D.], Belgian Science Policy Office, Interuniversity Attraction Poles Programme [IAP P7/28 to P.V.D.], Medical Research Council New Investigator Award [G0400284 to C.A.M.], MRC Centre for Medical Mycology and the University of Aberdeen [MR/M026663/1], FINSysB Consortium PhD Fellowship [PITN-GA-2008-214004 to V.C.], DIM-MalInf Région Ile-de-France PhD Fellowship (to A.N.), C. albicans ORFeome Project Post-doctoral Fellowship [WT088858MA to E.P.], NPARI Consortium Postdoctoral Fellowship [LSHE-CT-2006-037692 to T.R.], Programme Fungi from Institut Carnot-Pasteur Maladies Infectieuses Postdoctoral Fellowship (to U.Z.), FINSysB Post-doctoral Fellowship [PITN-GA-2008-214004 to S.Z.], KANJI consortia Post-doctoral Fellowship [ANR-08-MIE-033-01 to S.Z.], KU Leuven CREA Grant [2011-2013 to H.T.], France Génomique Consortium [ANR10-INBS-09-08], French Government’s Investissement d’Avenir program (Laboratoire d’Excellence Integrative Biology of Emerging Infectious Diseases) [ANR-10-LABX-62-IBEID]. Funding for open access charge: Institutional (Institut Pasteur)., ANR-08-MIEN-0033,KANJI,Colonisation et invasion de la muqueuse digestive par le champignon pathogène de l'homme Candida albicans(2008), ANR-10-PATH-0008,CANDICOL(2010), ANR-10-INBS-0009,France-Génomique,Organisation et montée en puissance d'une Infrastructure Nationale de Génomique(2010), ANR-10-LABX-0062,IBEID,Integrative Biology of Emerging Infectious Diseases(2010), European Project: 214004,PEOPLE,FP7-PEOPLE-2007-1-1-ITN,FINSYSB(2008), Institut Pasteur [Paris], Institut National de la Recherche Agronomique (INRA), Université Catholique de Louvain (UCL), Université Sorbonne Paris Cité (COMUE) (USPC), MICrobiologie de l'ALImentation au Service de la Santé (MICALIS), Institut National de la Recherche Agronomique (INRA)-AgroParisTech, Université Paris Saclay (COmUE), Biologie et Pathogénicité fongiques (BPF), Institut National de la Recherche Agronomique (INRA)-Institut Pasteur [Paris] (IP), Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Institut Pasteur [Paris] (IP)-Institut Pasteur [Paris] (IP), Bachellier- Bassi, Sophie, D'Enfert, Christophe, Institut National de la Recherche Agronomique (INRA)-Institut Pasteur [Paris], Centre National de la Recherche Scientifique (CNRS)-Institut Pasteur [Paris], ANR: ANR-10-INBS-09-08,The 'France Génomique' consortium, ANR-10-LABX-62-IBEID,IBEID,Laboratoire d'Excellence 'Integrative Biology of Emerging Infectious Diseases'(2010), and Bachellier-Bassi, Sophie
Subjects: 0301 basic medicine, [SDV]Life Sciences [q-bio], 030106 microbiology, Genetic Vectors, Genomics, Computational biology, Genome, Pathogenesis, Open Reading Frames, 03 medical and health sciences, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, [SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], Candida albicans, Protein Interaction Mapping, Genetics, Vector (molecular biology), ORFS, ORFeome, Gene, 030304 developmental biology, 0303 health sciences, biology, 030302 biochemistry & molecular biology, biology.organism_classification, Corpus albicans, Open reading frame, 030104 developmental biology, Databases, Nucleic Acid, Function (biology)
Abstract: The advent of the genomic era has made elucidating gene function at large scale a pressing challenge. ORFeome collections, whereby almost all ORFs of a given species are cloned and can be subsequently leveraged in multiple functional genomic approaches, represent valuable resources towards this endeavor. Here we provide novel, genome-scale tools for the study ofCandida albicans, a commensal yeast that is also responsible for frequent superficial and disseminated infections in humans. We have generated an ORFeome collection composed of 5,102 ORFs cloned in a Gateway™donor vector, representing 83% of the currently annotated coding sequences ofC. albicans. Sequencing data of the cloned ORFs are available in the CandidaOrfDB database athttp://candidaorfeome.eu. We also engineered 49 expression vectors with a choice of promoters, tags, and selection markers and demonstrated their applicability to the study of target ORFs transferred from theC. albicansORFeome. In addition, the use of the ORFeome in the detection of protein-protein interaction was demonstrated. Mating-compatible strains as well as Gateway™-compatible two-hybrid vectors were engineered, validated and used in a proof of concept experiment. These unique and valuable resources should greatly facilitate future functional studies inC. albicansand the elucidation of mechanisms that underlie its pathogenicity.
Published: 2018
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15. Core genome sequencing and genotyping of Leptospira interrogans in clinical samples by target capture sequencing

Author: Linda Grillova, Thomas Cokelaer, Jean-François Mariet, Juliana Pipoli da Fonseca, Mathieu Picardeau, Biologie des Spirochètes / Biology of Spirochetes, Université Paris Cité (UPCité)-Microbiologie Intégrative et Moléculaire (UMR6047), Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre National de Référence de la Leptospirose - National Reference Center Leptospirosis (CNR), Institut Pasteur [Paris] (IP)-Université Paris Cité (UPCité), Biomics (plateforme technologique), Hub Bioinformatique et Biostatistique - Bioinformatics and Biostatistics HUB, This work was supported by the Institut Pasteur through grant PTR 30-2017 and Santé Publique France to MP. TC and JP (Biomics Platform, C2RT, Institut Pasteur, Paris, France), supported by France Génomique (ANR-10-INBS-09) and IBISA., and ANR-10-INBS-0009,France-Génomique,Organisation et montée en puissance d'une Infrastructure Nationale de Génomique(2010)
Subjects: Leptospira, MESH: Genotype, Genotyping, MESH: Leptospira interrogans, Infectious Diseases, MESH: Humans, [SDV]Life Sciences [q-bio], Leptospirosis, MESH: Animals, Genomics, MESH: Leptospirosis, MESH: Zoonoses, MESH: Leptospira
Abstract: Background The life-threatening pathogen Leptospira interrogans is the most common agent of leptospirosis, an emerging zoonotic disease. However, little is known about the strains that are currently circulating worldwide due to the fastidious nature of the bacteria and the difficulty to isolate cultures. In addition, the paucity of bacteria in blood and other clinical samples has proven to be a considerable challenge for directly genotyping the agent of leptospirosis directly from patient material. Our understanding of the genetic diversity of strains during human infection is therefore limited. Methods Here, we carried out hybridization capture followed by Illumina sequencing of the core genome directly from 20 clinical samples that were PCR positive for pathogenic Leptospira to elucidate the genetic diversity of currently circulating Leptospira strains in mainland France. Results Capture with RNA probes covering the L. interrogans core genome resulted in a 72 to 13,000-fold increase in pathogen reads relative to standard sequencing without capture. Variant analysis of the genomes sequenced from the biological samples using 273 Leptospira reference genomes was then carried out to determine the genotype of the infecting strain. For samples with sufficient coverage (19/20 samples with coverage > 8×), we could unambiguously identify L. interrogans serovars Icterohaemorrhagiae and Copenhageni (14 samples), L. kirschneri serovar Grippotyphosa (4 samples), and L. interrogans serovar Pyrogenes (1 sample) as the infecting strains. Conclusions We obtained high-quality genomic data with suitable coverage for confident core genome genotyping of the agent of leptospirosis for most of our clinical samples. The recovery of the genome of the serovars Icterohaemorrhagiae and Copenhageni directly from multiple clinical samples revealed low adaptive diversification of the core genes during human infection. The ability to generate culture-free genomic data opens new opportunities for better understanding of the epidemiology of this fastidious pathogen and pathogenesis of this neglected disease.
Published: 2023
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16. A penicillin and metronidazole resistant Clostridium botulinum strain responsible for an infant botulism case

Author: Christelle Mazuet, Eun-Jeong Yoon, Christiane Bouchier, Sophie Boyer, Stéphanie Pignier, Martine Pestel-Caron, Djalal Meziane-Cherif, Clémentine Dumant-Forest, Michel R. Popoff, Christine Legeay, Isabelle Doehring, Patrice Courvalin, Philippe Bouvet, Jean Sautereau, Thierry Blanc, Suzana Quijano-Roy, Bactéries anaérobies et Toxines, Institut Pasteur [Paris], Agents antibactériens, Hôpital Charles Nicolle, Hôpital Charles Nicolle - CHU Rouen, Hôpital Raymond Poincaré, Assistance publique - Hôpitaux de Paris (AP-HP) - Hôpital Raymond Poincaré - Université Paris Descartes - Paris 5 (UPD5), Génomique (Plate-Forme), Centre de références maladies neuromusculaires, CHU Raymond Poincaré, Sequencing was performed at the GenomicsPlatform, member of 'France Génomique' consortium (ANR10-INBS-09-08).This work was supported by Institut Pasteur, Institut national de Veille Sanitaire, and byan unrestricted grant from Reckitt Benckiser., Groupe de Recherche sur les Antimicrobiens et les Micro-Organismes (GRAM 1.0), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU), Service de pédiatrie médicale et médecine de l'adolescent [Rouen], CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU), Service de pédiatrie néonatale et réanimation - neuropédiatrie [CHU Rouen], Hôpital Charles Nicolle [Rouen]-CHU Rouen, Hôpital Raymond Poincaré [AP-HP], Génomique (Plate-Forme) - Genomics Platform, Handicap neuromusculaire : Physiopathologie, Biothérapie et Pharmacologies appliquées (END-ICAP), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Institut National de la Santé et de la Recherche Médicale (INSERM), Filière Neuromusculaire (FILNEMUS), Sequencing was performed at the Genomics Platform, member of 'France Génomique' consortium (ANR10-INBS-09-08). This work was supported by Institut Pasteur, Institut national de Veille Sanitaire, and by an unrestricted grant from Reckitt Benckiser., ANR-10-INBS-0009,France-Génomique,Organisation et montée en puissance d'une Infrastructure Nationale de Génomique(2010), Institut Pasteur [Paris] (IP), Hôpital Charles Nicolle [Rouen], and Normandie Université (NU)-Normandie Université (NU)-CHU Rouen
Subjects: 0301 basic medicine, Microbiology (medical), infant botulism, Botulinum Toxins, medicine.drug_class, 030106 microbiology, Antibiotics, Microbial Sensitivity Tests, Penicillins, Biology, medicine.disease_cause, Microbiology, 03 medical and health sciences, Feces, Antibiotic resistance, metronidazole, Drug Resistance, Bacterial, Genes, Regulator, medicine, Clostridium botulinum, Humans, Botulism, Etest, botulism, Infant Botulism, Infant, Membrane Transport Proteins, General Medicine, Sequence Analysis, DNA, Penicillinase, medicine.disease, Virology, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, 3. Good health, Anti-Bacterial Agents, Penicillin, Metronidazole, Infectious Diseases, antibiotic-resistance, penicillin, Multigene Family, Female, [SDV.MP.BAC] Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, Genome, Bacterial, medicine.drug
Abstract: International audience; An infant botulism clinical course was characterized by several relapses despite therapy with amoxicillin and metronidazole. Botulism was confirmed by identification of botulinum toxin and C. botulinum in stools. A C. botulinum A2 strain resistant to penicillins and with heterogeneous resistance to metronidazole was isolated from stool samples up to 110 days after onset. Antibiotic susceptibility was tested by disk agar diffusion and minimum inhibitory concentrations were determined by Etest. Whole genome sequencing allowed detection of a gene cluster composed of blaCBP for a novel penicillinase, blaI for a regulator, and blaR1 for a membrane bound penicillin receptor in the chromosome of the C. botulinum isolate. The purified recombinant penicillinase was assayed. Resistance to β-lactams was in agreement with the kinetic parameters of the enzyme. In addition, the β-lactamase gene cluster was found in three C. botulinum genomes in databanks and in two out of 62 genomes of our collection, all the strains belonging to group I C. botulinum. This is the first report of a C. botulinum isolate resistant to penicillins. This stresses the importance of antibiotic susceptibility testing for adequate therapy of botulism.
Published: 2016
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17. Phages against Noncapsulated Klebsiella pneumoniae: Broader Host range, Slower Resistance

Author: Lourenço, Marta, Osbelt, Lisa, Passet, Virginie, Gravey, François, Megrian, Daniela, Strowig, Till, Rodrigues, Carla, Brisse, Sylvain, Biodiversité et Epidémiologie des Bactéries pathogènes - Biodiversity and Epidemiology of Bacterial Pathogens, Institut Pasteur [Paris] (IP)-Université Paris Cité (UPCité), Helmholtz Centre for Infection Research (HZI), German Center for Infection Research - partner site Hannover-Braunschweig (DZIF), Dynamique Microbienne associée aux Infections Urinaires et Respiratoires (DYNAMICURE), Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Microbiologie structurale - Structural Microbiology (Microb. Struc. (UMR_3528 / U-Pasteur_5)), Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), This work was mainly supported by the Joint Programming Initiative on Antimicrobial Resistance (JPIAMR) project CRISPR-ATTACK (Advancing CRISPR antimicrobials to combat the bacterial pathogen Klebsiella pneumoniae) under the French Agence Nationale de la Recherche grant ANR-18-JAM2-0004-04, S.B. and 01KI1824 to T.S. C.R. was also supported financially by a Pasteur-Roux fellowship by the Institut Pasteur. The BEBP laboratory is supported by the French Government Investissement d’Avenir Program Laboratoire d’Excellence, Integrative Biology of Emerging Infectious Diseases (ANR10LABX62IBEID). T.S. was also supported by the Federal Ministry of Science under the project DF-AMR2:DECOLONIZE (01KI2131), JPI-AMR Germany (01KI1824) as well as by the German Center for Infection Research (DZIF, TTU 06.826)., We thank Olaya Rendueles Garcia and Eduardo Rocha for sharing the mutant strains that were used for the anti-Kd phage isolation. We thank the Biomics Platform, C2RT, Institut Pasteur, Paris, France, supported by France Génomique (ANR-10-INBS-09-09) and IBISA, especially Marc Monot, Elodie Turc, Laure Lemée and Georges Haustant, for the sequencing project management, the preparation of the genomic libraries, and the sequencing. We thank Melanie Hennart for the bioinformatics methodological input and Anne-Marie Wehenkel for the help with the protein analyses. We are grateful to Jin-Town Wang for sharing the strain NTUH-K2044. We thank Quentin Lamy-Besnier, Chiara Crestani, and Olaya Rendueles Garcia for the critical reading of the manuscript., ANR-18-JAM2-0004,CRISPRattacK(2018), and ANR-10-LABX-0062,IBEID,Integrative Biology of Emerging Infectious Diseases(2010)
Subjects: Klebsiella pneumoniae, in vivo, bacteriophages, phage therapy, bacteriophage-bacteria interactions, phage resistance, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, genomics, host range, bacteriophage therapy, antimicrobial resistance, noncapsulated mutants, phage-bacteria interactions
Abstract: International audience; Klebsiella pneumoniae (Kp), a human gut colonizer and opportunistic pathogen, is a major contributor to the global burden of antimicrobial resistance. Virulent bacteriophages represent promising agents for decolonization and therapy. However, the majority of anti-Kp phages that have been isolated thus far are highly specific to unique capsular types (anti-K phages), which is a major limitation to phage therapy prospects due to the highly polymorphic capsule of Kp. Here, we report on an original anti-Kp phage isolation strategy, using capsule-deficient Kp mutants as hosts (anti-Kd phages). We show that anti-Kd phages have a broad host range, as the majority are able to infect noncapsulated mutants of multiple genetic sublineages and O-types. Additionally, anti-Kd phages induce a lower rate of resistance emergence in vitro and provide increased killing efficiency when in combination with anti-K phages. In vivo, anti-Kd phages are able to replicate in mouse guts colonized with a capsulated Kp strain, suggesting the presence of noncapsulated Kp subpopulations. The original strategy proposed here represents a promising avenue that circumvents the Kp capsule host restriction barrier, offering promise for therapeutic development.IMPORTANCE Klebsiella pneumoniae (Kp) is an ecologically generalist bacterium as well as an opportunistic pathogen that is responsible for hospital-acquired infections and a major contributor to the global burden of antimicrobial resistance. In the last decades, limited advances have been made in the use of virulent phages as alternatives or complements to antibiotics that are used to treat Kp infections. This work demonstrates the potential value of an anti-Klebsiella phage isolation strategy that addresses the issue of the narrow host range of anti-K phages. Anti-Kd phages may be active in infection sites in which capsule expression is intermittent or repressed or in combination with anti-K phages, which often induce the loss of capsule in escape mutants.
Published: 2023
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18. Chromosome folding and prophage activation reveal specific genomic architecture for intestinal bacteria

Author: Lamy-Besnier, Quentin, Bignaud, Amaury, Garneau, Julian, Titecat, Marie, Conti, Devon, von Strempel, Alexandra, Monot, Marc, Stecher, Bärbel, Koszul, Romain, Debarbieux, Laurent, Marbouty, Martial, Bactériophage, bactérie, hôte - Bacteriophage, bacterium, host, Université Paris Cité (UPCité)-Microbiologie Intégrative et Moléculaire (UMR6047), Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Régulation spatiale des Génomes - Spatial Regulation of Genomes, Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Collège Doctoral, Sorbonne Université (SU), Biomics (plateforme technologique), Institut Pasteur [Paris] (IP)-Université Paris Cité (UPCité), Institute for Translational Research in Inflammation - U 1286 (INFINITE (Ex-Liric)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), CHU Lille, Max Von Pettenkofer Institute (MVP), Ludwig-Maximilians-Universität München (LMU), German Center for Infection Research, Partnersite Munich (DZIF), This research was supported by funding to BS from DFG-STE-1971/11–1 (PhaStGut project), to BS from the European Research Council under the Horizon 2020 Program (ERC grant agreement 865615), to LD and MMa from PRCI ANR-20-CE92-0048 (PhaStGut project), and to RK from the European Research Council under the Horizon 2020 Program (ERC grant agreement 771813) and from JPI-EC-AMR STARCS ANR-16-JPEC-0003–05. QLB received funding from École Doctorale FIRE-Program Bettencourt. AB is supported by an ENS fellowship from the French Ministry of Higher Education, Research and Innovation. MMo and JRG were supported by JCJC ANR-18-CE35-0011 (project CDPhages). MT received funding from DigestScience. Biomics Platform, C2RT, Institut Pasteur, Paris, France, was supported by France Génomique (ANR-10-INBS-09) and IBISA. AB and DC belong to Ecole Doctorale Complexité du vivant ED515 of Sorbonne Université., ANR-20-CE92-0048,PhaStGut,Etude des mécanismes de la coexistence stable entre bactériophages et bactéries et de ses conséquences sur la fonction du microbiote intestinal(2020), ANR-16-JPEC-0003,STARCS,Selection and Transmission of Antimicrobial Resistance in Complex Systems(2016), ANR-18-CE35-0011,CDPhages,Le role des bactériophages dans l'évolution de la virulence chez Clostridium difficile(2018), ANR-10-INBS-0009,France-Génomique,Organisation et montée en puissance d'une Infrastructure Nationale de Génomique(2010), and European Project: 771813,ERC-2017-COG,SynarchiC(2018)
Subjects: Microbiology (medical), MESH: Humans, Virome, MESH: Genomics, [SDV.BBM.BM]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology, OMM12, Phages Gut HiC Virome OMM12 3D signatures, Microbiology, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, MESH: Bacteria, MESH: Prophages, 3D signatures, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, Phages, Gut, MESH: Animals, MESH: Ecosystem, MESH: Chromosomes, MESH: Bacteriophages, HiC, MESH: Mice
Abstract: Background Bacteria and their viruses, bacteriophages, are the most abundant entities of the gut microbiota, a complex community of microorganisms associated with human health and disease. In this ecosystem, the interactions between these two key components are still largely unknown. In particular, the impact of the gut environment on bacteria and their associated prophages is yet to be deciphered. Results To gain insight into the activity of lysogenic bacteriophages within the context of their host genomes, we performed proximity ligation-based sequencing (Hi-C) in both in vitro and in vivo conditions on the 12 bacterial strains of the OMM12 synthetic bacterial community stably associated within mice gut (gnotobiotic mouse line OMM12). High-resolution contact maps of the chromosome 3D organization of the bacterial genomes revealed a wide diversity of architectures, differences between environments, and an overall stability over time in the gut of mice. The DNA contacts pointed at 3D signatures of prophages leading to 16 of them being predicted as functional. We also identified circularization signals and observed different 3D patterns between in vitro and in vivo conditions. Concurrent virome analysis showed that 11 of these prophages produced viral particles and that OMM12 mice do not carry other intestinal viruses. Conclusions The precise identification by Hi-C of functional and active prophages within bacterial communities will unlock the study of interactions between bacteriophages and bacteria across conditions (healthy vs disease).
Published: 2023
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19. Extracellular succinate induces spatially organized biofilm formation in Clostridioides difficile

Author: Emile Auria, Julien Deschamps, Romain Briandet, Bruno Dupuy, Pathogénèse des Bactéries Anaérobies / Pathogenesis of Bacterial Anaerobes (PBA (U-Pasteur_6)), Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), MICrobiologie de l'ALImentation au Service de la Santé (MICALIS), AgroParisTech-Université Paris-Saclay-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), This work was funded by the Institut Pasteur, the 'Integrative Biology of Emerging Infectious Diseases' (LabEx IBEID) funded in the framework of the French Government’s 'Programme Investissements d’Avenir' and The ANR DifBioRel AAPCE5. EA is a doctoral fellow of Université Paris-Cité. We thank Juliana Pipoli Da Fonseca and Marc Monot for their help in acquiring the transcriptomic data within the Biomics Platform (C2RT, Institut Pasteur, Paris, France, supported by France Génomique (ANR-10-INBS-09) and IBISA)., ANR-10-LABX-0062,IBEID,Integrative Biology of Emerging Infectious Diseases(2010), ANR-20-CE15-0022,DifBioRel,Etude de la formation de biofilm par Clostridium difficile et de sa contribution dans la persistance intestinale de la bactérie et les rechutes des infections(2020), and ANR-10-INBS-0009,France-Génomique,Organisation et montée en puissance d'une Infrastructure Nationale de Génomique(2010)
Subjects: Succinate, Clostridioides difficile, Biofilm, Microbiota, [SDV]Life Sciences [q-bio], [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, Cell Biology, Molecular Biology, Applied Microbiology and Biotechnology, Microbiology
Abstract: International audience; Clostridioides difficile infection associated to gut microbiome dysbiosis is the leading cause for nosocomial diarrhea. The ability of C. difficile to form biofilms has been progressively linked to its pathogenesis as well as its persistence in the gut. Although C. difficile has been reported to form biofilms in an increasing number of conditions, little is known about how these biofilms are formed in the gut and what factors may trigger their formation. Here we report that succinate, a metabolite abundantly produced by the dysbiotic gut microbiota, induces in vitro biofilm formation of C. difficile strains. We characterized the morphology and spatial composition of succinate-induced biofilms, and compared to non-induced or deoxycholate (DCA) induced biofilms. Biofilms induced by succinate are significantly thicker, structurally more complex, and poorer in proteins and exopolysaccharides (EPS). We then applied transcriptomics and genetics to characterize the early stages of succinate-induced biofilm formation and we showed that succinate-induced biofilm results from major metabolic shifts and cell-wall composition changes. Similar to DCA-induced biofilms, biofilms induced by succinate depend on the presence of a rapidly metabolized sugar. Finally, although succinate can be consumed by the bacteria, we found that the extracellular succinate is in fact responsible for the induction of biofilm formation through complex regulation involving global metabolic regulators and the osmotic stress response. Thus, our work suggests that as a gut signal, succinate may drive biofilm formation and help persistence of C. difficile in the gut, increasing the risk of relapse.
Published: 2023
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20. Escherichia coli Aggregates Mediated by Native or Synthetic Adhesins Exhibit Both Core and Adhesin-Specific Transcriptional Responses

Author: Yankel Chekli, Rebecca J. Stevick, Etienne Kornobis, Valérie Briolat, Jean-Marc Ghigo, Christophe Beloin, Génétique des Biofilms - Genetics of Biofilms, Université Paris Cité (UPCité)-Microbiologie Intégrative et Moléculaire (UMR6047), Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Hub Bioinformatique et Biostatistique - Bioinformatics and Biostatistics HUB, Institut Pasteur [Paris] (IP)-Université Paris Cité (UPCité), Biomics (plateforme technologique), This work was supported by grants from the French Government’s Investissement d’Avenir program, Laboratoire d’Excellence Integrative Biology of Emerging Infectious Diseases (grant no. ANR-10-LABX-62-IBEID) and by the Fondation pour la Recherche Médicale (grant no. DEQ20180339185). Y.C. was supported by a MENESR (Ministère Français de l’Education Nationale, de l’Enseignement Supérieur et de la Recherche) fellowship. R.J.S. was supported by a grant from the Philippe Foundation. Biomics Platform -C2RT- was supported by France Génomique (grant no. ANR-10-INBS-09-09) and IBISA., ANR-10-LABX-0062,IBEID,Integrative Biology of Emerging Infectious Diseases(2010), and ANR-10-INBS-0009,France-Génomique,Organisation et montée en puissance d'une Infrastructure Nationale de Génomique(2010)
Subjects: Microbiology (medical), tolerance, stress tolerance, General Immunology and Microbiology, Ecology, Physiology, [SDV]Life Sciences [q-bio], E. coli, antigen 43, stress response, Cell Biology, nanobodies, anaerobia, bacterial physiology, Infectious Diseases, Escherichia coli, aggregates, Genetics, Ag43
Abstract: International audience; Bacteria can rapidly tune their physiology and metabolism to adapt to environmental fluctuations. In particular, they can adapt their lifestyle to the close proximity of other bacteria or the presence of different surfaces. However, whether these interactions trigger transcriptomic responses is poorly understood. We used a specific setup of E. coli strains expressing native or synthetic adhesins mediating bacterial aggregation to study the transcriptomic changes of aggregated compared to nonaggregated bacteria. Our results show that, following aggregation, bacteria exhibit a core response independent of the adhesin type, with differential expression of 56.9% of the coding genome, including genes involved in stress response and anaerobic lifestyle. Moreover, when aggregates were formed via a naturally expressed E. coli adhesin (antigen 43), the transcriptomic response of the bacteria was more exaggerated than that of aggregates formed via a synthetic adhesin. This suggests that the response to aggregation induced by native E. coli adhesins could have been finely tuned during bacterial evolution. Our study therefore provides insights into the effect of self-interaction in bacteria and allows a better understanding of why bacterial aggregates exhibit increased stress tolerance.IMPORTANCE The formation of bacterial aggregates has an important role in both clinical and ecological contexts. Although these structures have been previously shown to be more resistant to stressful conditions, the genetic basis of this stress tolerance associated with the aggregate lifestyle is poorly understood. Surface sensing mediated by different adhesins can result in various changes in bacterial physiology. However, whether adhesin-adhesin interactions, as well as the type of adhesin mediating aggregation, affect bacterial cell physiology is unknown. By sequencing the transcriptomes of aggregated and nonaggregated cells expressing native or synthetic adhesins, we characterized the effects of aggregation and adhesin type on E. coli physiology.
Published: 2023
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21. BioConvert: a comprehensive format converter for life sciences

Author: Hugo Caro, Sulyvan Dollin, Anne Biton, Bryan Brancotte, Dimitri Desvillechabrol, Yoann Dufresne, Blaise Li, Etienne Kornobis, Frédéric Lemoine, Nicolas Maillet, Amandine Perrin, Nicolas Traut, Bertrand Néron, Thomas Cokelaer, Biomics (plateforme technologique), Institut Pasteur [Paris] (IP)-Université Paris Cité (UPCité), Hub Bioinformatique et Biostatistique - Bioinformatics and Biostatistics HUB, Algorithmes pour les séquences biologiques - Sequence Bioinformatics, Génomique évolutive des virus à ARN - Evolutionary genomics of RNA viruses, Génomique évolutive des Microbes / Microbial Evolutionary Genomics, Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Neuroanatomie Appliquée et Théorique / Applied and Theoretical Neuroanatomy (NAAT), France Génomique Consortium (ANR 10-INBS-09-08) and IBISA and the Biomics Platform of Institut Pasteur, Paris, France, and ANR-10-INBS-0009,France-Génomique,Organisation et montée en puissance d'une Infrastructure Nationale de Génomique(2010)
Subjects: [INFO.INFO-DS]Computer Science [cs]/Data Structures and Algorithms [cs.DS], [INFO.INFO-BI]Computer Science [cs]/Bioinformatics [q-bio.QM]
Abstract: Bioinformatics is a field known for the numerous standards and formats that have been developed over the years. This plethora of formats, sometimes complementary, and often redundant, poses many challenges to bioinformatics data analysts. They constantly need to find the best tool to convert their data into the suitable format, which is often a complex, technical and time consuming task. Moreover, these small yet important tasks are often difficult to make reproducible. To over-come these difficulties, we initiatedBioConvert, a collaborative project to facilitate the conversion of life science data from one format to another.BioConvertaggregates existing software within a single framework and complemented them with original code when needed. It provides a common interface to make the user experience more streamlined instead of having to learn tens of them. Currently,BioConvertsupports about 50 formats and 100 direct conversions in areas such as alignment, sequencing, phylogeny, and variant calling. In addition to being useful for end-users,BioConvertcan also be utilized by developers as a universal benchmarking framework for evaluating and comparing numerous conversion tools. Additionally, we provide a web server implementing an online user-friendly interface toBioConvert, hence allowing direct use for the community.
Published: 2023
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22. SARS‐CoV‐2‐related bat virus behavior in human‐relevant models sheds light on the origin of COVID‐19

Author: Sarah Temmam, Xavier Montagutelli, Cécile Herate, Flora Donati, Béatrice Regnault, Mikael Attia, Eduard Baquero Salazar, Delphine Chretien, Laurine Conquet, Grégory Jouvion, Juliana Pipoli Da Fonseca, Thomas Cokelaer, Faustine Amara, Francis Relouzat, Thibaut Naninck, Julien Lemaitre, Nathalie Derreudre‐Bosquet, Quentin Pascal, Massimiliano Bonomi, Thomas Bigot, Sandie Munier, Felix A Rey, Roger Le Grand, Sylvie van der Werf, Marc Eloit, Découverte de pathogènes – Pathogen discovery, Institut Pasteur [Paris] (IP)-Université Paris Cité (UPCité), Centre Collaborateur de l'OIE de Détection et identification chez l’homme des pathogènes animaux émergents et développement d’outils pour leur diagnostic / Collaborating Center for the Detection and identification in humans of emerging animal pathogens and development of tools for their diagnoses (CCOIE-OIECC), Institut Pasteur [Paris] (IP)-Organisation Mondiale de la Santé Animale / World Organisation Animal Health [Paris] (OIE)-Université Paris Cité (UPCité), Génétique de la souris - Mouse Genetics, Immunologie des maladies virales, auto-immunes, hématologiques et bactériennes (IMVA-HB), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, Génétique Moléculaire des Virus à ARN - Molecular Genetics of RNA Viruses (GMV-ARN (UMR_3569 / U-Pasteur_2)), Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Centre National de Référence des virus des infections respiratoires (dont la grippe) - National Reference Center Virus Influenzae [Paris] (CNR - laboratoire coordonnateur), Virologie Structurale - Structural Virology, École nationale vétérinaire - Alfort (ENVA), Dynamic Microbiology - EA 7380 (DYNAMIC), École nationale vétérinaire - Alfort (ENVA)-Agence nationale de sécurité sanitaire de l'alimentation, de l'environnement et du travail (ANSES)-Université Paris-Est (UPE)-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Biomics (plateforme technologique), Bioinformatique structurale - Structural Bioinformatics, Hub Bioinformatique et Biostatistique - Bioinformatics and Biostatistics HUB, Next-generation sequencing was performed with the help of Biomics Platform, C2RT, Institut Pasteur, Paris, France, supported by France Génomique (ANR-10-INBS-09-09), IBISA, and the Illumina COVID-19 Projects' offer. The work was funded by an Institut Pasteur 'Covid Taskforce' and in part by the H2020 project 101003589 (RECOVER) and Labex IBEID (ANR-10-LABX62-IBEID) grants. The Infectious Disease Models and Innovative Therapies (IDMIT) research infrastructure is supported by the 'Programme Investissements d'Avenir', managed by the ANR under reference ANR-11-INBS-0008. The Fondation Bettencourt Schueller and the Region Ile-de-France contributed to the implementation of IDMIT's facilities and imaging technologies. The NHP model of SARS-CoV-2 infection have been developed thanks to the support from REACTing, the Fondation pour la Recherche Medicale (FRM, AM-CoV-Path)., ANR-10-INBS-0009,France-Génomique,Organisation et montée en puissance d'une Infrastructure Nationale de Génomique(2010), ANR-10-LABX-0062,IBEID,Integrative Biology of Emerging Infectious Diseases(2010), ANR-11-INBS-0008,IDMIT,Infrastructure nationale pour la modélisation des maladies infectieuses humaines(2011), and European Project: 101003589, H2020-SC1-PHE-CORONAVIRUS-2020,RECOVER(2020)
Subjects: animal model, pathogenesis, [SDE]Environmental Sciences, Genetics, adaptive mutations, serology, bat coronavirus, Molecular Biology, Biochemistry
Abstract: International audience; Bat sarbecovirus BANAL-236 is highly related to SARS-CoV-2 and infects human cells, albeit lacking the furin cleavage site in its spike protein. BANAL-236 replicates efficiently and pauci-symptomatically in humanized mice and in macaques, where its tropism is enteric, strongly differing from that of SARS-CoV-2. BANAL-236 infection leads to protection against superinfection by a virulent strain. We find no evidence of antibodies recognizing bat sarbecoviruses in populations in close contact with bats in which the virus was identified, indicating that such spillover infections, if they occur, are rare. Six passages in humanized mice or in human intestinal cells, mimicking putative early spillover events, select adaptive mutations without appearance of a furin cleavage site and no change in virulence. Therefore, acquisition of a furin site in the spike protein is likely a pre-spillover event that did not occur upon replication of a SARS-CoV-2-like bat virus in humans or other animals. Other hypotheses regarding the origin of the SARS-CoV-2 should therefore be evaluated, including the presence of sarbecoviruses carrying a spike with a furin cleavage site in bats.
Published: 2023
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23. Stepwise use of genomics and transcriptomics technologies increases diagnostic yield in Mendelian disorders

Author: Estelle Colin, Yannis Duffourd, Martin Chevarin, Emilie Tisserant, Simon Verdez, Julien Paccaud, Ange-Line Bruel, Frédéric Tran Mau-Them, Anne-Sophie Denommé-Pichon, Julien Thevenon, Hana Safraou, Thomas Besnard, Alice Goldenberg, Benjamin Cogné, Bertrand Isidor, Julian Delanne, Arthur Sorlin, Sébastien Moutton, Mélanie Fradin, Christèle Dubourg, Magali Gorce, Dominique Bonneau, Salima El Chehadeh, François-Guillaume Debray, Martine Doco-Fenzy, Kevin Uguen, Nicolas Chatron, Bernard Aral, Nathalie Marle, Paul Kuentz, Anne Boland, Robert Olaso, Jean-François Deleuze, Damien Sanlaville, Patrick Callier, Christophe Philippe, Christel Thauvin-Robinet, Laurence Faivre, Antonio Vitobello, Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM), Lipides - Nutrition - Cancer [Dijon - U1231] (LNC), Université de Bourgogne (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Agro Dijon, Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro), FHU TRANSLAD (CHU de Dijon), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Equipe GAD (LNC - U1231), Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Université de Bourgogne (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Agro Dijon, CHU Dijon, Centre hospitalier universitaire de Nantes (CHU Nantes), Nantes Université (Nantes Univ), Institut du Thorax [Nantes], Département de génétique [CHU Rouen] (Centre Normandie de Génomique et de Médecine Personnalisée), CHU Rouen, Normandie Université (NU)-Normandie Université (NU), Génomique et Médecine Personnalisée du Cancer et des Maladies Neuropsychiatriques (GPMCND), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Pontchaillou [Rennes], Centre de référence Maladies Rares CLAD-Ouest [Rennes], Institut de Génétique et Développement de Rennes (IGDR), Université de Rennes (UR)-Centre National de la Recherche Scientifique (CNRS)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Hémostase et Remodelage Vasculaire Post-Ischémie (HERVI - EA 3801), Université de Reims Champagne-Ardenne (URCA), Hospices Civils de Lyon (HCL), Génétique, génomique fonctionnelle et biotechnologies (UMR 1078) (GGB), EFS-Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Brestois Santé Agro Matière (IBSAM), Université de Brest (UBO), Centre National de Recherche en Génomique Humaine (CNRGH), Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Laboratory of Excellence GENMED [Paris] (Medical Genomics), This work was supported by grants from Dijon University Hospital, the ISITE-BFC (PIA ANR), the European Union through the FEDER programs (PERSONALISE), and the Burgundy-Franche Comté regional council (INTEGRA). The sequencing performed at the CNRGH was supported by the France Génomique National infrastructure, funded as part of the 'Investissements d’Avenir' program managed by the Agence Nationale pour la Recherche (contract ANR-10-INBS-09)., and ANR-10-INBS-0009,France-Génomique,Organisation et montée en puissance d'une Infrastructure Nationale de Génomique(2010)
Subjects: [SDV.GEN.GH]Life Sciences [q-bio]/Genetics/Human genetics, Cell Biology, Developmental Biology
Abstract: Purpose: Multi-omics offer worthwhile and increasingly accessible technologies to diagnostic laboratories seeking potential second-tier strategies to help patients with unresolved rare diseases, especially patients clinically diagnosed with a rare OMIM (Online Mendelian Inheritance in Man) disease. However, no consensus exists regarding the optimal diagnostic care pathway to adopt after negative results with standard approaches.Methods: In 15 unsolved individuals clinically diagnosed with recognizable OMIM diseases but with negative or inconclusive first-line genetic results, we explored the utility of a multi-step approach using several novel omics technologies to establish a molecular diagnosis. Inclusion criteria included a clinical autosomal recessive disease diagnosis and single heterozygous pathogenic variant in the gene of interest identified by first-line analysis (60%–9/15) or a clinical diagnosis of an X-linked recessive or autosomal dominant disease with no causative variant identified (40%–6/15). We performed a multi-step analysis involving short-read genome sequencing (srGS) and complementary approaches such as mRNA sequencing (mRNA-seq), long-read genome sequencing (lrG), or optical genome mapping (oGM) selected according to the outcome of the GS analysis.Results: SrGS alone or in combination with additional genomic and/or transcriptomic technologies allowed us to resolve 87% of individuals by identifying single nucleotide variants/indels missed by first-line targeted tests, identifying variants affecting transcription, or structural variants sometimes requiring lrGS or oGM for their characterization.Conclusion: Hypothesis-driven implementation of combined omics technologies is particularly effective in identifying molecular etiologies. In this study, we detail our experience of the implementation of genomics and transcriptomics technologies in a pilot cohort of previously investigated patients with a typical clinical diagnosis without molecular etiology.
Published: 2023
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24. Golgi localization of SARS-CoV-2 spike protein and interaction with furin in cerebral COVID-19 microangiopathy: a clue to the central nervous system involvement?

Author: Boluda, Susana, Mokhtari, Karima, Mégarbane, Bruno, Annane, Djillali, Mathon, Bertrand, Cao, Albert, Adam, Clovis, Androuin, Alexandre, Bielle, Franck, Brochier, Guy, Charlotte, Frédéric, Chougar, Lydia, El Hachimi, Khalid Hamid, Eloit, Marc, Haïk, Stéphane, Hervé, Dominique, Kasri, Amal, Leducq, Valentin, Lehéricy, Stéphane, Levavasseur, Etienne, Lobsiger, Christian, Lorin De La Grandmaison, Geoffroy, Malet, Isabelle, Malissin, Isabelle, Marot, Stéphane, Marty, Serge, Pérot, Philippe, Plu, Isabelle, Prigent, Annick, Stimmer, Lev, Potier, Marie-Claude, Marcelin, Anne-Geneviève, Delatour, Benoît, Duyckaerts, Charles, Seilhean, Danielle, Institut du Cerveau = Paris Brain Institute (ICM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Optimisation thérapeutique en Neuropsychopharmacologie (OPTeN (UMR_S_1144 / U1144)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Hôpital Lariboisière-Fernand-Widal [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Hôpital Raymond Poincaré [Garches], Université Paris-Saclay, Infection et inflammation (2I), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), AP-HP Hôpital Bicêtre (Le Kremlin-Bicêtre), Institut de Myologie, Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Association française contre les myopathies (AFM-Téléthon)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), École Pratique des Hautes Études (EPHE), Université Paris sciences et lettres (PSL), Découverte de pathogènes – Pathogen discovery, Institut Pasteur [Paris] (IP), Université Sorbonne Paris Nord, Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), The authors thank the Cohort COVID-19 Neurosciences (CoCo Neurosciences) study supported by APHP and funded by the generous support of the Federation Internationale de l’Automobile (FIA), the FIA Foundation and donors of Paris Brain Institute – ICM. The research leading to these results has received funding from Sorbonne University (PathoCoV project) and from the program 'Investissements d’avenir' ANR-10- IAIHU-06. This work benefited from equipment and services from the CELIS cell culture core facility (Paris Brain Institute), a platform receiving support from ANR-10- IAIHU-06 and ANR-11-INBS-0011-NeurATRIS. We thank for targeted NGS sequencing the Biomics Platform, C2RT, Institut Pasteur, Paris, France, supported by France Génomique (ANR-10-INBS-09-09), IBISA and the Illumina COVID-19 Projects’ offer., ANR-10-IAHU-0006,IHU-A-ICM,Institut de Neurosciences Translationnelles de Paris(2010), ANR-11-INBS-0011,NeurATRIS,Infrastructure de Recherche Translationnelle pour les Biothérapies en Neurosciences(2011), and ANR-10-INBS-0009,France-Génomique,Organisation et montée en puissance d'une Infrastructure Nationale de Génomique(2010)
Subjects: Furin, Blood-brain barrier (BBB), Original Paper, Microangiopathy, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, Neuro-Covid, [SDV.MHEP.AHA]Life Sciences [q-bio]/Human health and pathology/Tissues and Organs [q-bio.TO], COVID-19
Abstract: In a neuropathological series of 20 COVID-19 cases, we analyzed six cases (three biopsies and three autopsies) with multiple foci predominantly affecting the white matter as shown by MRI. The cases presented with microhemorrhages evocative of small artery diseases. This COVID-19 associated cerebral microangiopathy (CCM) was characterized by perivascular changes: arterioles were surrounded by vacuolized tissue, clustered macrophages, large axonal swellings and a crown arrangement of aquaporin-4 immunoreactivity. There was evidence of blood-brain-barrier leakage. Fibrinoid necrosis, vascular occlusion, perivascular cuffing and demyelination were absent. While no viral particle or viral RNA was found in the brain, the SARS-CoV-2 spike protein was detected in the Golgi apparatus of brain endothelial cells where it closely associated with furin, a host protease known to play a key role in virus replication. Endothelial cells in culture were not permissive to SARS-CoV-2 replication. The distribution of the spike protein in brain endothelial cells differed from that observed in pneumocytes. In the latter, the diffuse cytoplasmic labeling suggested a complete replication cycle with viral release, notably through the lysosomal pathway. In contrast, in cerebral endothelial cells the excretion cycle was blocked in the Golgi apparatus. Interruption of the excretion cycle could explain the difficulty of SARS-CoV-2 to infect endothelial cells in vitro and to produce viral RNA in the brain. Specific metabolism of the virus in brain endothelial cells could weaken the cell walls and eventually lead to the characteristic lesions of COVID-19 associated cerebral microangiopathy. Furin as a modulator of vascular permeability could provide some clues for the control of late effects of microangiopathy., Free Neuropathology, Vol. 4 (2023)
Published: 2023
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25. Genome structures resolve the early diversification of teleost fishes

Author: Elise Parey, Alexandra Louis, Jerome Montfort, Olivier Bouchez, Céline Roques, Carole Iampietro, Jerome Lluch, Adrien Castinel, Cécile Donnadieu, Thomas Desvignes, Christabel Floi Bucao, Elodie Jouanno, Ming Wen, Sahar Mejri, Ron Dirks, Hans Jansen, Christiaan Henkel, Wei-Jen Chen, Margot Zahm, Cédric Cabau, Christophe Klopp, Andrew W. Thompson, Marc Robinson-Rechavi, Ingo Braasch, Guillaume Lecointre, Julien Bobe, John H. Postlethwait, Camille Berthelot, Hugues Roest Crollius, Yann Guiguen, Laboratoire de Physiologie et Génomique des Poissons (LPGP), Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique )-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Institut de biologie de l'ENS Paris (IBENS), Département de Biologie - ENS Paris, École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Génome et Transcriptome - Plateforme Génomique ( GeT-PlaGe), Plateforme Génome & Transcriptome (GET), Génopole Toulouse Midi-Pyrénées [Auzeville] (GENOTOUL), Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Ecole Nationale Vétérinaire de Toulouse (ENVT), Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Génopole Toulouse Midi-Pyrénées [Auzeville] (GENOTOUL), Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), University of Oregon [Eugene], Université de Lausanne = University of Lausanne (UNIL), Swiss Institute of Bioinformatics [Lausanne] (SIB), Hunan Normal University (HNU), Florida Atlantic University [Boca Raton], Future Genomics Technologies, Universiteit Leiden, Norwegian University of Life Sciences (NMBU), National Taiwan University [Taiwan] (NTU), Génétique Physiologie et Systèmes d'Elevage (GenPhySE ), Ecole Nationale Vétérinaire de Toulouse (ENVT), Université de Toulouse (UT)-Université de Toulouse (UT)-École nationale supérieure agronomique de Toulouse (ENSAT), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Système d'Information des GENomes des Animaux d'Elevage (SIGENAE), Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Unité de Mathématiques et Informatique Appliquées de Toulouse (MIAT INRAE), Western Michigan University [Kalamazoo], Michigan State University [East Lansing], Michigan State University System, Institut de Systématique, Evolution, Biodiversité (ISYEB ), Muséum national d'Histoire naturelle (MNHN)-École Pratique des Hautes Études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Université des Antilles (UA), Génomique fonctionnelle comparative - Comparative functional genomics, Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), This work was supported by the Agence Nationale de la Recherche, France (ANR) on the GenoFish project, 2016–2021 (grant No. ANR-16-CE12-003) to H.R.C., C.B., J.B., J.H.P., M.R.C., and Y.G., and by France Génomique National infrastructure, funded as part of 'Investissement d’avenir' program managed by ANR (grant No. ANR-10-INBS-09) to C.D. Part of the fellowship to E.P. was supported by funds from the European Union Horizon 2020 research and innovation program under Grant Agreement No 817923 (AQUA-FAANG). M.R.-R. was supported by the Swiss National Science Foundation grant 31003A_173048. J.H.P and I.B were supported by the National Institutes of Health under grant agreement No. R01OD011116. W.J.C. was supported by MOST grants No. 111-2611-M-002-025, 110-2611-M-002-013, and 108-2611-M-002-012-MY2., ANR-16-CE12-0035,GenoFish,Evolution des génes et des génomes après duplication compléte(2016), ANR-10-INBS-0009,France-Génomique,Organisation et montée en puissance d'une Infrastructure Nationale de Génomique(2010), European Project: 817923,H2020,H2020-EU.3.2.1.1., H2020-EU.3.2.3.1.,AQUA-FAANG(2019), DYnamique et Organisation des GENomes - Equipe de l'IBENS (DYOGEN), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Département de Biologie - ENS Paris, Institute of Oceanography [Taipei], Plateforme Bio-Informatique - Génotoul, Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Unité de Mathématiques et Informatique Appliquées de Toulouse (MIAT INRAE), Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-BioInfOmics, Génétique des génomes - Genetics of Genomes (UMR 3525), Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Swiss National Science Foundation grant 31003A_173048, National Institute of Health under grant agreement No R01OD011116, and Muséum national d'Histoire naturelle (MNHN)
Subjects: Animals, Zebrafish/genetics, Fishes/genetics, Eels/genetics, Biological Evolution, Phylogeny, Genome, Evolution, Molecular, Multidisciplinary, [SDV]Life Sciences [q-bio], [SDV.BA.ZV]Life Sciences [q-bio]/Animal biology/Vertebrate Zoology, [SDV.BID]Life Sciences [q-bio]/Biodiversity
Abstract: Accurate species phylogenies are a prerequisite for evolutionary research. Teleosts are by far the largest and the most diversified group of extant vertebrates, but relationships among the three oldest lineages of extant teleosts remain unresolved. Based on seven high-quality new genome assemblies in Elopomorpha (tarpons, eels), we revisited the topology of the deepest branches of the teleost phylogeny using independent gene sequence and chromosomal rearrangement phylogenomic approaches. These analyses converged to a single scenario that unambiguously places the Elopomorpha and Osteoglossomorpha (bony-tongues) in a monophyletic group sister to all other teleosts, i.e., the Clupeocephala lineage. This finding resolves over 50 years of controversy on the evolutionary relationships of these lineages and highlights the power of combining different levels of genome-wide information to solve complex phylogenies.One-Sentence SummaryWhole-genome analyses place Elopomorpha (tarpons, eels) and Osteoglossomorpha (bony-tongues) as sister groups at the deepest branching of crown teleosts.
Published: 2023
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26. Peroxisomal defects in microglial cells induce a disease-associated microglial signature

Author: Quentin Raas, Ali Tawbeh, Mounia Tahri-Joutey, Catherine Gondcaille, Céline Keime, Romain Kaiser, Doriane Trompier, Boubker Nasser, Valerio Leoni, Emma Bellanger, Maud Boussand, Yannick Hamon, Alexandre Benani, Francesca Di Cara, Caroline Truntzer, Mustapha Cherkaoui-Malki, Pierre Andreoletti, Stéphane Savary, Raas, Q, Tawbeh, A, Tahri-Joutey, M, Gondcaille, C, Keime, C, Kaiser, R, Trompier, D, Nasser, B, Leoni, V, Bellanger, E, Boussand, M, Hamon, Y, Benani, A, Di Cara, F, Truntzer, C, Cherkaoui-Malki, M, Andreoletti, P, Savary, S, Laboratoire Bio-PeroxIL. Biochimie du peroxysome, inflammation et métabolisme lipidique [Dijon] (BIO-PEROXIL), Université de Bourgogne (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Bourgogne Franche-Comté [COMUE] (UBFC), Faculty of Science and Technology, University Hassan I, Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Università degli Studi di Milano-Bicocca = University of Milano-Bicocca (UNIMIB), Mi-mAbs (C/O CIML), Centre d'Immunologie de Marseille - Luminy (CIML), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre des Sciences du Goût et de l'Alimentation [Dijon] (CSGA), Université de Bourgogne (UB)-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Institut Agro Dijon, Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro), Université Bourgogne Franche-Comté [COMUE] (UBFC), Dalhousie University [Halifax], Centre Régional de Lutte contre le cancer Georges-François Leclerc [Dijon] (UNICANCER/CRLCC-CGFL), UNICANCER, We warmly acknowledge the Fondation Maladies Rares which supported our transcriptomic analysis project (GenOmics: High throughput sequencing and rare diseases, call 2017-20170615). Sequencing was performed by the GenomEast platform, a member of the 'France Génomique' consortium (ANR-10-INBS-0009). We would like to acknowledge the SATT Sayens of Dijon, the CHU of Dijon (project CRBSEP-EMATSEP grant), the Canadian New Frontiers Research Funds Exploration (NFRF-E 19-00007), and the regional council of Bourgogne Franche-Comté (Project PERSIL 2019) for their support. We are also grateful to networking support by the COST Action CA 16,112 NutRedOx (Personalized Nutrition in aging society: redox control of major age-related diseases), supported by COST (European Cooperation in Science and Technology). We thank the Centre d’Immunologie de Marseille-Luminy (CIML) flow cytometry facility. This work was supported by institutional grants from INSERM, CNRS and Aix-Marseille University to the CIML and program grant from the French National Research Agency (ANR-17-CE15-0032). The project leading to this publication has received funding from Excellence Initiative of Aix-Marseille University—A*MIDEX, a French 'Investissements d’Avenir' program. The laboratory BioPeroxIL was funded by the Ministère de l’Education Nationale et de l’Enseignement Supérieur et de la Recherche (France) and by the University of Bourgogne. MT-J was funded by CNRST (PhD excellence grant number: 17UHP2019, Morocco) and by the Action Intégrée of the Comité Mixte Inter-universitaire Franco-Marocain (n° TBK 19/92 n° Campus France: 41501RJ) from the PHC Toubkal program, Ministère des Affaires Étrangères., ANR-10-INBS-0009,France-Génomique,Organisation et montée en puissance d'une Infrastructure Nationale de Génomique(2010), and ANR-17-CE15-0032,NanoGammaR,Comprendre comment la dynamique membranaire du récepteur à l'IFN-gamma à l'échelle nanométrique contrôle les réponses immunes médiées par l'IFN-gamma(2017)
Subjects: Cellular and Molecular Neuroscience, autophagy, [SCCO.NEUR]Cognitive science/Neuroscience, lipid metabolism, [SDV.MHEP.PHY]Life Sciences [q-bio]/Human health and pathology/Tissues and Organs [q-bio.TO], adrenoleukodystrophy (X-ALD), lysosome, microglia, peroxisome, Molecular Biology
Abstract: International audience; Microglial cells ensure essential roles in brain homeostasis. In pathological condition, microglia adopt a common signature, called disease-associated microglial (DAM) signature, characterized by the loss of homeostatic genes and the induction of disease-associated genes. In X-linked adrenoleukodystrophy (X-ALD), the most common peroxisomal disease, microglial defect has been shown to precede myelin degradation and may actively contribute to the neurodegenerative process. We previously established BV-2 microglial cell models bearing mutations in peroxisomal genes that recapitulate some of the hallmarks of the peroxisomal β-oxidation defects such as very long-chain fatty acid (VLCFA) accumulation. In these cell lines, we used RNA-sequencing and identified large-scale reprogramming for genes involved in lipid metabolism, immune response, cell signaling, lysosome and autophagy, as well as a DAM-like signature. We highlighted cholesterol accumulation in plasma membranes and observed autophagy patterns in the cell mutants. We confirmed the upregulation or downregulation at the protein level for a few selected genes that mostly corroborated our observations and clearly demonstrated increased expression and secretion of DAM proteins in the BV-2 mutant cells. In conclusion, the peroxisomal defects in microglial cells not only impact on VLCFA metabolism but also force microglial cells to adopt a pathological phenotype likely representing a key contributor to the pathogenesis of peroxisomal disorders.
Published: 2023
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27. First chromosome scale genomes of ithomiine butterflies (Nymphalidae: Ithomiini): comparative models for mimicry genetic studies

Author: Jérémy Gauthier, Joana Meier, Fabrice Legeai, Melanie McClure, Annabel Whibley, Anthony Bretaudeau, Hélène Boulain, Hugues Parrinello, Sam T. Mugford, Richard Durbin, Chenxi Zhou, Shane McCarthy, Christopher W. Wheat, Florence Piron‐Prunier, Christelle Monsempes, Marie‐Christine François, Paul Jay, Camille Noûs, Emma Persyn, Emmanuelle Jacquin‐Joly, Camille Meslin, Nicolas Montagné, Claire Lemaitre, Marianne Elias, Natural History Museum [Geneva], Department of Zoology [Cambridge], University of Cambridge [UK] (CAM), Institut de Génétique, Environnement et Protection des Plantes (IGEPP), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Institut Agro Rennes Angers, Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro), Institut de Recherche en Informatique et Systèmes Aléatoires (IRISA), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National des Sciences Appliquées - Rennes (INSA Rennes), Institut National des Sciences Appliquées (INSA)-Université de Rennes (UNIV-RENNES)-Institut National des Sciences Appliquées (INSA)-Université de Bretagne Sud (UBS)-École normale supérieure - Rennes (ENS Rennes)-Institut National de Recherche en Informatique et en Automatique (Inria)-CentraleSupélec-Centre National de la Recherche Scientifique (CNRS)-IMT Atlantique (IMT Atlantique), Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT), Scalable, Optimized and Parallel Algorithms for Genomics (GenScale), Inria Rennes – Bretagne Atlantique, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria)-GESTION DES DONNÉES ET DE LA CONNAISSANCE (IRISA-D7), Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT)-Université de Rennes 1 (UR1), Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT)-Institut de Recherche en Informatique et Systèmes Aléatoires (IRISA), Institut National des Sciences Appliquées (INSA)-Université de Rennes (UNIV-RENNES)-Institut National des Sciences Appliquées (INSA)-Université de Bretagne Sud (UBS)-École normale supérieure - Rennes (ENS Rennes)-CentraleSupélec-Centre National de la Recherche Scientifique (CNRS)-IMT Atlantique (IMT Atlantique), Institut de Systématique, Evolution, Biodiversité (ISYEB ), Muséum national d'Histoire naturelle (MNHN)-École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Université des Antilles (UA), Laboratoire Ecologie, Evolution, Interactions des Systèmes amazoniens (LEEISA), Institut Français de Recherche pour l'Exploitation de la Mer (IFREMER)-Université de Guyane (UG)-Centre National de la Recherche Scientifique (CNRS), School of Biological Sciences [Auckland], University of Auckland [Auckland], Department of Ecology and Evolution [Lausanne], Université de Lausanne = University of Lausanne (UNIL), Institut de Génomique Fonctionnelle - Montpellier GenomiX (IGF MGX), Institut de Génomique Fonctionnelle (IGF), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM)-BioCampus (BCM), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), John Innes Centre [Norwich], Biotechnology and Biological Sciences Research Council (BBSRC), Department of Crop Genetics, Biotechnology and Biological Sciences Research Council (BBSRC)-Biotechnology and Biological Sciences Research Council (BBSRC), Department of Genetics [Cambridge], The Wellcome Trust Sanger Institute [Cambridge], Stockholm University, Institut d'écologie et des sciences de l'environnement de Paris (iEES Paris ), Institut de Recherche pour le Développement (IRD)-Sorbonne Université (SU)-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Ecologie Systématique et Evolution (ESE), AgroParisTech-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS), Laboratoire Cogitamus, Peuplements végétaux et bioagresseurs en milieu tropical (UMR PVBMT), Centre de Coopération Internationale en Recherche Agronomique pour le Développement (Cirad)-Institut de Recherche pour le Développement (IRD)-Université de La Réunion (UR)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), ME acknowledges financial support from ANR (projects SPECREP, ANR-14-CE02-0011, and CLEARWING, ANR-16-CE02-0012) and HFSP (RGP0014/2016). MGX acknowledges financial support from France Génomique National infrastructure, funded as part of 'Investissement d’Avenir' program managed by Agence Nationale pour la Recherche (contract ANR-10-INBS-0009). RD, SM and CZ acknowledge financial support from Wellcome grant WT207492, and SM and work at the Wellcome Sanger Institute were also supported by Wellcome grant WT206194. We thank members of the Wellcome Sanger Institute Scientific Operations and Tree of Life core groups for their contributions to data production and assembly for the Melinaea genomes. We thank Mario Tuanama and Ronald Mori-Pezo for help with rearing and collecting butterflies. MM acknowledges a postdoctoral fellowship by the Fonds Québécois de la Recherche sur la Nature et les Technologies (FQRNT). STM acknowledges support from the BBSRC Institute Strategy Programme (BB/P012574/1). We thank the Peruvian authorities for research permits (236-2012-AG-DGFFS-DGEFFS, 201-2013-MINAGRI-DGFFS/DGEFFS, 002-2015-SERFOR-DGGSPFFS and 373-2017-SERFOR-DGGSPFFS), the Gobierno Regional San Martín PEHCBM (permit: 124-2016-GRSM/PEHCBM-DMA/EII-ANP/JARR) and the Museo de Historia Natural and Prof. Gerardo Lamas for their support. We thank the GenOuest BioInformatics Platform (http://www.genouest.org), which allowed the use of a computing cluster for bioinformatic analyses., ANR-14-CE02-0011,SPECREP,Répétabilité du processus de spéciation chez les papillons: replications naturelles dans une zone de suture(2014), ANR-16-CE02-0012,CLEARWING,La transparence : origine physique, fonctions adaptatives et évolution chez les papillons transparents(2016), ANR-10-INBS-0009,France-Génomique,Organisation et montée en puissance d'une Infrastructure Nationale de Génomique(2010), Gauthier, Jérémy [0000-0001-6666-1002], Meier, Joana [0000-0001-7726-2875], Whibley, Annabel [0000-0003-1878-7705], Parrinello, Hugues [0000-0002-1151-001X], Wheat, Christopher W [0000-0003-1863-2340], Apollo - University of Cambridge Repository, Université de Rennes (UR)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Institut Agro Rennes Angers, Université de Rennes (UR)-Institut National des Sciences Appliquées - Rennes (INSA Rennes), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université de Bretagne Sud (UBS)-École normale supérieure - Rennes (ENS Rennes)-Institut National de Recherche en Informatique et en Automatique (Inria)-CentraleSupélec-Centre National de la Recherche Scientifique (CNRS)-IMT Atlantique (IMT Atlantique), Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT)-Université de Rennes (UR)-Institut National des Sciences Appliquées - Rennes (INSA Rennes), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université de Bretagne Sud (UBS)-École normale supérieure - Rennes (ENS Rennes)-CentraleSupélec-Centre National de la Recherche Scientifique (CNRS)-IMT Atlantique (IMT Atlantique), Muséum national d'Histoire naturelle (MNHN)-École Pratique des Hautes Études (EPHE), International Aphid Genomics Consortium (IAGC), Department of Crop Genetics [Norwich], and Department of Zoology [Stockholm]
Subjects: ithomiine butterflies, Genomics, chromosome-level genome, Adaptation, Physiological, Chromosomes, Phenotype, Hi-C, Genetics, Animals, [INFO.INFO-BI]Computer Science [cs]/Bioinformatics [q-bio.QM], Butterflies, Ecology, Evolution, Behavior and Systematics, mimicry, Biotechnology, Butterflies/genetics, Chromosomes/genetics, olfaction
Abstract: Funder: Human Frontier Science Program; Id: http://dx.doi.org/10.13039/501100000854, The ithomiine butterflies (Nymphalidae: Danainae) represent the largest known radiation of Müllerian mimetic butterflies. They dominate by number the mimetic butterfly communities, which include species such as the iconic neotropical Heliconius genus. Recent studies on the ecology and genetics of speciation in Ithomiini have suggested that sexual pheromones, colour pattern and perhaps hostplant could drive reproductive isolation. However, no reference genome was available for Ithomiini, which has hindered further exploration on the genetic architecture of these candidate traits, and more generally on the genomic patterns of divergence. Here, we generated high-quality, chromosome-scale genome assemblies for two Melinaea species, M. marsaeus and M. menophilus, and a draft genome of the species Ithomia salapia. We obtained genomes with a size ranging from 396 to 503 Mb across the three species and scaffold N50 of 40.5 and 23.2 Mb for the two chromosome-scale assemblies. Using collinearity analyses we identified massive rearrangements between the two closely related Melinaea species. An annotation of transposable elements and gene content was performed, as well as a specialist annotation to target chemosensory genes, which is crucial for host plant detection and mate recognition in mimetic species. A comparative genomic approach revealed independent gene expansions in ithomiines and particularly in gustatory receptor genes. These first three genomes of ithomiine mimetic butterflies constitute a valuable addition and a welcome comparison to existing biological models such as Heliconius, and will enable further understanding of the mechanisms of adaptation in butterflies.
Published: 2023
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28. Natural mutations in the sensor kinase of the PhoPR two-component regulatory system modulate virulence of ancestor-like tuberculosis bacilli

Author: Malaga, Wladimir, Payros, Delphine, Meunier, Eva, Frigui, Wafa, Sayes, Fadel, Pawlik, Alexandre, Orgeur, Mickael, Berrone, Céline, Moreau, Flavie, Mazères, Serge, Gonzalo-Asensio, Jesus, Rengel, David, Martin, Carlos, Astarie-Dequeker, Catherine, Mourey, Lionel, Brosch, Roland, Guilhot, Christophe, Institut de pharmacologie et de biologie structurale (IPBS), Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Centre National de la Recherche Scientifique (CNRS), Pathogénomique mycobactérienne intégrée - Integrated Mycobacterial Pathogenomics, Université Paris Cité (UPCité)-Microbiologie Intégrative et Moléculaire (UMR6047), Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), University of Zaragoza - Universidad de Zaragoza [Zaragoza], Instituto de Salud Carlos III [Madrid, Spain] (ISCIII), This project has received funding from the Agence Nationale pour la Recherche (ANR-20-CE15-0013) to C.G., R.B. and L.M., the Fondation Bettencourt Schueller (www.fondationbs.org) to C.G. and the Fondation MSDAvenir (evenement.msdavenir.fr) to C.G. This work was supported by grants from the French Ministry of Research (Programme Investissement d’Avenir, PIA, Equipex ANINIMIP ANR-11-EQUIPEX-0003 to C.G. and & ANR-10-LABX-62-IBEID to R.B.). The Biomics Platform is supported by France Génomique (ANR-10-INBS-09-09) and IBISA., e authors acknowledge support from the GenoToul (Toulouse, France) Biostatistics platform, the Anexplo platform for animal experimentation and the TRI platform for imaging. The authors thank Samantha Milia for technical assistance at the Experimental Histopathology Facility of the INSERM / UPS US006 CREFRE, Toulouse Purpan, France. The authors thank Elodie Turc and Marc Monot (Biomics Platform, C2RT, Institut Pasteur, Paris, France) for processing the RNA sequencing., ANR-20-CE15-0013,MTB-Spread,PhoPR et transmission de la tuberculose(2020), ANR-10-LABX-0062,IBEID,Integrative Biology of Emerging Infectious Diseases(2010), and ANR-10-INBS-0009,France-Génomique,Organisation et montée en puissance d'une Infrastructure Nationale de Génomique(2010)
Subjects: [SDV.BBM.BM]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology
Abstract: International audience; The molecular factors and genetic adaptations that contributed to the emergence of Mycobacterium tuberculosis (MTB) from an environmental Mycobacterium canettii -like ancestor, remain poorly investigated. In MTB , the PhoPR two-component regulatory system controls production and secretion of proteins and lipid virulence effectors. Here, we describe that several mutations, present in phoR of M . canettii relative to MTB , impact the expression of the PhoP regulon and the pathogenicity of the strains. First, we establish a molecular model of PhoR and show that some substitutions found in PhoR of M . canettii are likely to impact the structure and activity of this protein. Second, we show that STB-K, the most attenuated available M . canettii strain, displays lower expression of PhoP-induced genes than MTB . Third, we demonstrate that genetic swapping of the phoPR allele from STB-K with the ortholog from MTB H37Rv enhances expression of PhoP-controlled functions and the capacities of the recombinant strain to colonize human macrophages, the MTB target cells, as well as to cause disease in several mouse infection models. Fourth, we extended these observations to other M . canettii strains and confirm that PhoP-controlled functions are expressed at lower levels in most M . canettii strains than in M . tuberculosis . Our findings suggest that distinct PhoR variants have been selected during the evolution of tuberculosis bacilli, contributing to higher pathogenicity and persistence of MTB in the mammalian host.
Published: 2023
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29. Capturing SARS-CoV-2 from patient samples with low viral abundance: a comparative analysis

Author: Juliana, Pipoli da Fonseca, Etienne, Kornobis, Elodie, Turc, Vincent, Enouf, Laure, Lemée, Thomas, Cokelaer, Marc, Monot, Biomics (plateforme technologique), Institut Pasteur [Paris] (IP)-Université Paris Cité (UPCité), Hub Bioinformatique et Biostatistique - Bioinformatics and Biostatistics HUB, Génétique Moléculaire des Virus à ARN - Molecular Genetics of RNA Viruses (GMV-ARN (UMR_3569 / U-Pasteur_2)), Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Centre National de Référence des virus des infections respiratoires (dont la grippe) - National Reference Center Virus Influenzae [Paris] (CNR - laboratoire coordonnateur), Pasteur International Bioresources network (PIBNet), We thank the Biomics Platform, C2RT, Institut Pasteur, Paris, France, supported by France Génomique (ANR-10-INBS-09), IBISA, and the Illumina COVID-19 Project. This work was supported by the 'URGENCE COVID-19' fundraising campaign of the Institut Pasteur., A special thanks also to the other members of Biomics who allowed the project to continue during lockdown: L. Ma, G. Haustant, Z. Allouche, V. Briolat, I. Najjar, L. Motreff, and A. Etienne., and ANR-10-INBS-0009,France-Génomique,Organisation et montée en puissance d'une Infrastructure Nationale de Génomique(2010)
Subjects: COVID-19 Testing, Multidisciplinary, Base Sequence, SARS-CoV-2, [SDV]Life Sciences [q-bio], Humans, COVID-19, Genome, Viral, Pandemics
Abstract: Since the beginning of the SARS-CoV-2 coronavirus pandemic, genome sequencing is essential to monitor viral mutations over time and by territory. This need for complete genetic information is further reinforced by the rapid spread of variants of concern. In this paper, we assess the ability of the hybridization technique, Capture-Seq, to detect the SARS-CoV-2 genome, either partially or in its integrity on patients samples. We studied 20 patient nasal swab samples broken down into five series of four samples of equivalent viral load from CT25 to CT36+. For this, we tested 3 multi-virus panel as well as 2 SARS-CoV-2 only panels. The panels were chosen based on their specificity, global or specific, as well as their technological difference in the composition of the probes: ssRNA, ssDNA and dsDNA. The multi-virus panels are able to capture high-abundance targets but fail to capture the lowest-abundance targets, with a high percentage of off-target reads corresponding to the abundance of the host sequences. Both SARS-CoV-2-only panels were very effective, with high percentage of reads corresponding to the target. Overall, capture followed by sequencing is very effective for the study of SARS-CoV-2 in low-abundance patient samples and is suitable for samples with CT values up to 35.
Published: 2022
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30. Phage-Plasmids Spread Antibiotic Resistance Genes through Infection and Lysogenic Conversion

Author: Eduardo Rocha, Eugen Pfeifer, Rémy A. Bonnin, Génomique évolutive des Microbes / Microbial Evolutionary Genomics, Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Immunologie des maladies virales, auto-immunes, hématologiques et bactériennes (IMVA-HB), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, INCEPTION project (PIA/ANR-16-CONV-0005), Equipe FRM (Fondation pour la Recherche Médicale): EQU201903007835, Laboratoire d’Excellence IBEID Integrative Biology of Emerging Infectious Diseases [ANR-10-LABX-62-IBEID], SALMOPROPHAGE ANR-16-CE16-0029. Sequencing was done at the Biomics Platform, C2RT, Institut Pasteur, Paris, France and was supported by France Génomique (ANR-10-INBS-09) and IBISA., We especially thank Olaya Rendueles Garcia, Marc Monot, Goerges Haustant, Laure Lemée, Valérie Briolat, Laurence Ma, Elodie Turc, Amandine Buffet, and Matthieu Haudiquet for providing support, advice, and services regarding DNA isolation, library preparation, and sequencing. Moreover, we are grateful to the strain collection center of the Institut Pasteur for great service and for efficiently providing the strains that we used in our study. This work used the computational and storage services (TARS & MAESTRO cluster) provided by the IT department at Institut Pasteur, Paris., ANR-16-CONV-0005,INCEPTION,Institut Convergences pour l'étude de l'Emergence des Pathologies au Travers des Individus et des populatiONs(2016), ANR-10-LABX-0062,IBEID,Integrative Biology of Emerging Infectious Diseases(2010), ANR-10-INBS-0009,France-Génomique,Organisation et montée en puissance d'une Infrastructure Nationale de Génomique(2010), ANR-16-CE12-0029,Salmo_prophages,Co-évolution des génomes bactériens et de leurs prophages: cooptation des prophages et conversion lysogenique chez Salmonella(2016), Eduardo, Rocha, Institut Convergences pour l'étude de l'Emergence des Pathologies au Travers des Individus et des populatiONs - - INCEPTION2016 - ANR-16-CONV-0005 - CONV - VALID, Integrative Biology of Emerging Infectious Diseases - - IBEID2010 - ANR-10-LABX-0062 - LABX - VALID, Organisation et montée en puissance d'une Infrastructure Nationale de Génomique - - France-Génomique2010 - ANR-10-INBS-0009 - INBS - VALID, and Co-évolution des génomes bactériens et de leurs prophages: cooptation des prophages et conversion lysogenique chez Salmonella - - Salmo_prophages2016 - ANR-16-CE12-0029 - AAPG2016 - VALID
Subjects: prophage induction, antibiotic resistance, Microbiology, beta-Lactamases, phage genomics, Virology, [SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], [SDV.BID.EVO] Life Sciences [q-bio]/Biodiversity/Populations and Evolution [q-bio.PE], Escherichia coli, Bacteriophages, [INFO.INFO-BI] Computer Science [cs]/Bioinformatics [q-bio.QM], [SDV.GEN.GPO]Life Sciences [q-bio]/Genetics/Populations and Evolution [q-bio.PE], [SDV.BIBS] Life Sciences [q-bio]/Quantitative Methods [q-bio.QM], Colistin, [SDV.BID.EVO]Life Sciences [q-bio]/Biodiversity/Populations and Evolution [q-bio.PE], Drug Resistance, Microbial, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, [SDV.BIBS]Life Sciences [q-bio]/Quantitative Methods [q-bio.QM], Anti-Bacterial Agents, Cephalosporins, Aminoglycosides, Carbapenems, [SDV.GEN.GPO] Life Sciences [q-bio]/Genetics/Populations and Evolution [q-bio.PE], DNA Transposable Elements, [SDV.BBM.GTP] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], integrons, [INFO.INFO-BI]Computer Science [cs]/Bioinformatics [q-bio.QM], [SDV.MP.BAC] Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, Plastics, Plasmids, Fluoroquinolones
Abstract: Antibiotic resistance is rapidly spreading by horizontal transfer of resistance genes in mobile genetic elements. While plasmids are key drivers of this process, very few integrative phages encode antibiotic resistance genes. Here, we find that phage-plasmids, elements that are both phages and plasmids, often carry antibiotic resistance genes. We found 60 phage-plasmids with 184 antibiotic resistance genes, including broad-spectrum-cephalosporins, carbapenems, aminoglycosides, fluoroquinolones and colistin. These genes are in a few hotspots, seem to have been co-translocated with transposable elements, and are often in class I integrons, which had not been previously found in phages. We tried to induce six phage-plasmids with resistance genes (including four with resistance integrons) and succeeded in five cases. Other phage-plasmids and integrative prophages were co-induced in these experiments. As a proof of principle, we focused on a P1-like element encoding an extended spectrum β-lactamase, blaCTX-M-55. After induction, we confirmed that it’s capable to infect and convert four other E. coli strains. Its re-induction led to further conversion of a sensitive strain, confirming it’s a fully functional phage. This study shows that phage-plasmids carry a large diversity of clinically relevant antibiotic resistance genes that they transfer across bacteria. As plasmids, these elements seem very plastic and capable of acquiring genes from other plasmids. As phages, they may provide novel paths of transfer for resistance genes, because they can infect bacteria distant in time and space from the original host. As a matter of alarm, they may also eventually mediate transfer to other types of phages.ImportanceDissemination of antimicrobial resistances is a major threat to global health. Here, we show that a group of temperate bacterial viruses (=phages), termed phage-plasmids, commonly encode different and multiple types of resistance genes of high clinical importance, often in integrons. This is unexpected since phages typically do not carry resistance genes and, hence, do not confer their hosts with resistance upon infection and genome integration. Our experiments with phage-plasmids isolated from clinical settings confirmed they infect sensitive strains, rendering them antibiotic resistant. The spread of antibiotic resistance genes by phage-plasmids is worrisome because it dispenses cell-to-cell contact, necessary for the canonical plasmid transfer (=conjugation). Furthermore, their integrons are now genetic platforms for the acquisition of novel resistance genes.
Published: 2022
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31. A Defect in Lipoprotein Modification by Lgt Leads to Abnormal Morphology and Cell Death in Escherichia coli That Is Independent of Major Lipoprotein Lpp

Author: S. Legood, D. Seng, I. G. Boneca, N. Buddelmeijer, Biologie et Génétique de la Paroi bactérienne - Biology and Genetics of Bacterial Cell Wall, Institut Pasteur [Paris] (IP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)-Microbiologie Intégrative et Moléculaire (UMR6047), Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), This work was financed by Institut Pasteur and the Pasteur Paris University (PPU)-Oxford International PhD Program with a fellowship to S.L.G. Our research received funding from the Institut Carnot Infectious Diseases Global Care (16 CARN 0023-01 Project iLiNT) and from the French Government’s Investissement d’Avenir program, Laboratoire d’Excellence 'Integrative Biology of Emerging Infectious Diseases' (grant ANR-10-LABX-62-IBEID)., We thank G. H. Haustant, L. Lemée, and M. Monot from the Biomics Platform, C2RT, Institut Pasteur, Paris, France, who are supported by France Génomique (ANR-10-INBS-09) and IBISA. We thank Sharookh Kapadia for strain MG1655Δlgt and Hajime Tokuda for Lpp antibodies. We are grateful for constructive comments and suggestions from all BGPB lab members., and ANR-10-LABX-0062,IBEID,Integrative Biology of Emerging Infectious Diseases(2010)
Subjects: cell envelope, Cell Death, Escherichia coli Proteins, Lipoproteins, viability, Lpp, Arabinose, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, Microbiology, Anti-Bacterial Agents, Transferases, Lgt, Escherichia coli, Humans, Molecular Biology, Escherichia coli Infections, cell viability, Bacterial Outer Membrane Proteins
Abstract: WGS data have been submitted to the NCBI SRA database under accession number PRJNA860548.; International audience; Lgt is an essential enzyme in proteobacteria and therefore a potential target for novel antibiotics. The effect of Lgt depletion on growth, morphology, and viability was studied in Escherichia coli to assess whether absence of Lgt leads to cell death. Two Lgt depletion strains were used in which lgt was under the control of an arabinose-inducible promoter that allowed regulation of Lgt protein levels. Reduced levels of Lgt led to severe growth and morphological defects that could be restored by expressing lgt in trans, demonstrating that only Lgt is responsible for the distorted phenotypes. In the absence of major lipoprotein Lpp, growth defects were partially restored when low levels of Lgt were still present; however, lgt could not be deleted in the absence of Lpp. Our results demonstrate that Lpp is not the main cause of cell death under conditions of Lgt depletion and that other lipoproteins are important in cell envelope biogenesis and cell viability. Specific inhibitors of Lgt are thus promising for the development of novel antibiotics. IMPORTANCE Incomplete maturation and envelope mislocalization of lipoproteins, through inhibition or mutations in lipoprotein modification enzymes or transport to the outer membrane, are lethal in proteobacteria. Resistance to small-molecule inhibition or the appearance of suppressor mutations is often directly correlated with the presence of abundant outer membrane lipoprotein Lpp. Our results show that Lgt, the first enzyme of the lipoprotein modification pathway, is still required for growth and viability in the absence of Lpp and thus is necessary for the function of other essential lipoproteins in the cell envelope. This adds credence to the hypothesis that Lgt is essential in proteobacteria and an attractive target for the development of novel antibiotics.
Published: 2022
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32. OMIXCARE: OMICS technologies solved about 33% of the patients with heterogeneous rare neuro-developmental disorders and negative exome sequencing results and identified 13% additional candidate variants

Author: Estelle Colin, Yannis Duffourd, Emilie Tisserant, Raissa Relator, Ange-Line Bruel, Frédéric Tran Mau-Them, Anne-Sophie Denommé-Pichon, Hana Safraou, Julian Delanne, Nolwenn Jean-Marçais, Boris Keren, Bertrand Isidor, Marie Vincent, Cyril Mignot, Delphine Heron, Alexandra Afenjar, Solveig Heide, Anne Faudet, Perrine Charles, Sylvie Odent, Yvan Herenger, Arthur Sorlin, Sébastien Moutton, Jennifer Kerkhof, Haley McConkey, Martin Chevarin, Charlotte Poë, Victor Couturier, Valentin Bourgeois, Patrick Callier, Anne Boland, Robert Olaso, Christophe Philippe, Bekim Sadikovic, Christel Thauvin-Robinet, Laurence Faivre, Jean-François Deleuze, Antonio Vitobello, Jonchère, Laurent, Organisation et montée en puissance d'une Infrastructure Nationale de Génomique - - France-Génomique2010 - ANR-10-INBS-0009 - INBS - VALID, Medical Genomics - - GENMED2010 - ANR-10-LABX-0013 - LABX - VALID, Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM), Lipides - Nutrition - Cancer [Dijon - U1231] (LNC), Université de Bourgogne (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Agro Dijon, Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro), FHU TRANSLAD (CHU de Dijon), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), London Health Sciences Center (LHSC), CHU Dijon, CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre hospitalier universitaire de Nantes (CHU Nantes), Institut du Cerveau = Paris Brain Institute (ICM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), CHU Trousseau [APHP], Sorbonne Université (SU), Institut de Génétique et Développement de Rennes (IGDR), Université de Rennes (UR)-Centre National de la Recherche Scientifique (CNRS)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), CHU Pontchaillou [Rennes], Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Centre National de Recherche en Génomique Humaine (CNRGH), Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Laboratory of Excellence GENMED [Paris] (Medical Genomics), University of Western Ontario (UWO), The study was performed within the framework of the GAD (Génétique des Anomalies du Développement) collection and approved by the appropriate institutional review board of Dijon University Hospital (DC2011-1332). This work was supported by grants from Dijon University Hospital, the ISITE-BFC (PIA ANR), the European Union through the FEDER programs (PERSONALISE), and the Burgundy-Franche-Compté regional council (INTEGRA). The sequencing platform at the CNRGH was supported by the France Génomique National infrastructure, funded as part of the 'Investissements d’Avenir' program, managed by the Agence Nationale pour la Recherche (contract ANR-10-INBS-09). The whole genome sequencing performed at the CNRGH was funded by the Laboratory of Excellence GENMED (Medical Genomics) Grant No. ANR-10-LABX-0013, managed by the National Research Agency (ANR) as part of the Investment for the Future program., ANR-10-INBS-0009,France-Génomique,Organisation et montée en puissance d'une Infrastructure Nationale de Génomique(2010), and ANR-10-LABX-0013,GENMED,Medical Genomics(2010)
Subjects: genome sequencing, DNA methylation analysis, [SDV.GEN]Life Sciences [q-bio]/Genetics, translational research, Cell Biology, [SDV.GEN] Life Sciences [q-bio]/Genetics, transcriptome sequencing, undiagnosed neurodevelopmental diseases, Developmental Biology
Abstract: Purpose: Patients with rare or ultra-rare genetic diseases, which affect 350 million people worldwide, may experience a diagnostic odyssey. High-throughput sequencing leads to an etiological diagnosis in up to 50% of individuals with heterogeneous neurodevelopmental or malformation disorders. There is a growing interest in additional omics technologies in translational research settings to examine the remaining unsolved cases.Methods: We gathered 30 individuals with malformation syndromes and/or severe neurodevelopmental disorders with negative trio exome sequencing and array comparative genomic hybridization results through a multicenter project. We applied short-read genome sequencing, total RNA sequencing, and DNA methylation analysis, in that order, as complementary translational research tools for a molecular diagnosis.Results: The cohort was mainly composed of pediatric individuals with a median age of 13.7 years (4 years and 6 months to 35 years and 1 month). Genome sequencing alone identified at least one variant with a high level of evidence of pathogenicity in 8/30 individuals (26.7%) and at least a candidate disease-causing variant in 7/30 other individuals (23.3%). RNA-seq data in 23 individuals allowed two additional individuals (8.7%) to be diagnosed, confirming the implication of two pathogenic variants (8.7%), and excluding one candidate variant (4.3%). Finally, DNA methylation analysis confirmed one diagnosis identified by genome sequencing (Kabuki syndrome) and identified an episignature compatible with a BAFopathy in a patient with a clinical diagnosis of Coffin-Siris with negative genome and RNA-seq results in blood.Conclusion: Overall, our integrated genome, transcriptome, and DNA methylation analysis solved 10/30 (33.3%) cases and identified a strong candidate gene in 4/30 (13.3%) of the patients with rare neurodevelopmental disorders and negative exome sequencing results.
Published: 2022
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33. SUPT3H-less SAGA coactivator can assemble and function without significantly perturbing RNA polymerase II transcription in mammalian cells

Author: Veronique Fischer, Vincent Hisler, Elisabeth Scheer, Elisabeth Lata, Bastien Morlet, Damien Plassard, Dominique Helmlinger, Didier Devys, László Tora, Stéphane D Vincent, Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Plateforme GenomEast [Illkrch], Infrastructure France Génomique, Centre de recherche en Biologie cellulaire de Montpellier (CRBM), Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM), and VINCENT, Stéphane
Subjects: Saccharomyces cerevisiae Proteins, Transcription, Genetic, Saccharomyces cerevisiae, DNA-Binding Proteins, Histones, Mice, Trans-Activators, Genetics, [SDV.BBM] Life Sciences [q-bio]/Biochemistry, Molecular Biology, Animals, Humans, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, RNA Polymerase II, Histone Acetyltransferases, Transcription Factors
Abstract: Coactivator complexes regulate chromatin accessibility and transcription. SAGA (Spt-Ada-Gcn5 Acetyltransferase) is an evolutionary conserved coactivator complex. The core module scaffolds the entire SAGA complex and adopts a histone octamer-like structure, which consists of six histone-fold domain (HFD)-containing proteins forming three histone-fold (HF) pairs, to which the double HFD-containing SUPT3H adds one HF pair. Spt3, the yeast ortholog of SUPT3H, interacts genetically and biochemically with the TATA binding protein (TBP) and contributes to global RNA polymerase II (Pol II) transcription. Here we demonstrate that (i) SAGA purified from human U2OS or mouse embryonic stem cells (mESC) can assemble without SUPT3H, (ii) SUPT3H is not essential for mESC survival, but required for their growth and self-renewal, and (iii) the loss of SUPT3H from mammalian cells affects the transcription of only a specific subset of genes. Accordingly, in the absence of SUPT3H no major change in TBP accumulation at gene promoters was observed. Thus, SUPT3H is not required for the assembly of SAGA, TBP recruitment, or overall Pol II transcription, but plays a role in mESC growth and self-renewal. Our data further suggest that yeast and mammalian SAGA complexes contribute to transcription regulation by distinct mechanisms.
Published: 2022
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34. Structure of the rabies virus glycoprotein trimer bound to a prefusion-specific neutralizing antibody

Author: Heather M. Callaway, Dawid Zyla, Florence Larrous, Guilherme Dias de Melo, Kathryn M. Hastie, Ruben Diaz Avalos, Alyssa Agarwal, Davide Corti, Hervé Bourhy, Erica Ollmann Saphire, La Jolla Institute for Immunology [La Jolla, CA, États-Unis], Institut Pasteur [Paris] (IP), Lyssavirus, épidémiologie et neuropathologie - Lyssavirus Epidemiology and Neuropathology, Institut Pasteur [Paris] (IP)-Université Paris Cité (UPCité), Humabs BioMed SA, University of California [San Diego] (UC San Diego), University of California (UC), This work was supported by National Institutes of Health (NIH) grants 5T32AI07244-36 (H.M.C.) and 5F32AI147531-03 (H.M.C.) and by Swiss National Science Foundation Early Postdoc Mobility Fellowship P2EZP3_195680 (D.Z.). A portion of this research was supported by NIH grant U24GM129547 and performed at the PNCC at OHSU and accessed through EMSL (grid.436923.9), a DOE Office of Science User Facility sponsored by the Office of Biological and Environmental Research. Confocal microscopy on the Zeiss LSM 880 was supported by equipment grant NIH S10OD021831., and We thank S. Schendel for manuscript editing and L. Kergoat (Lyssavirus Epidemiology and Neuropathology Unit, Institut Pasteur, Paris, France) for technical assistance with virus and mouse experiments. Part of this work was performed at the UtechS Photonic BioImaging (PBI) platform supported by Institut Pasteur and by Région Ile-de-France (program DIM1Health). We also thank G. M. Haustant and L. Lemée (Biomics Platform, C2RT, Institut Pasteur, Paris, France), supported by France Génomique (ANR-10-INBS-09), and IBISA for Illumina sequencing.
Subjects: Multidisciplinary, [SDV]Life Sciences [q-bio]
Abstract: International audience; Rabies infection is nearly 100% lethal if untreated and kills more than 50,000 people annually, many of them children. Existing rabies vaccines target the rabies virus glycoprotein (RABV-G) but generate short-lived immune responses, likely because the protein is heterogeneous under physiological conditions. Here, we report the 3.39 Å cryo–electron microscopy structure of trimeric, prefusion RABV-G complexed with RVA122, a potently neutralizing human antibody. RVA122 binds to a quaternary epitope at the top of RABV-G, bridging domains and stabilizing RABV-G protomers in a prefusion state. RABV-G trimerization involves side-to-side interactions between the central α helix and adjacent loops, rather than contacts between central helices, and interactions among the fusion loops at the glycoprotein base. These results provide a basis from which to develop improved rabies vaccines based on RABV-G stabilized in the prefusion conformation.
Published: 2022
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35. The extensive transgenerational transcriptomic effects of ocean acidification on the olfactory epithelium of a marine fish are associated with a better viral resistance

Author: Mishal Cohen-Rengifo, Morgane Danion, Anne-Alicia Gonzalez, Marie-Laure Bégout, Alexandre Cormier, Cyril Noël, Joëlle Cabon, Thomas Vitré, Felix C. Mark, David Mazurais, Institut Français de Recherche pour l'Exploitation de la Mer (IFREMER), Laboratoire de Ploufragan-Plouzané-Niort [ANSES], Agence nationale de sécurité sanitaire de l'alimentation, de l'environnement et du travail (ANSES), BioCampus (BCM), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM), MARine Biodiversity Exploitation and Conservation (UMR MARBEC), Institut de Recherche pour le Développement (IRD)-Institut Français de Recherche pour l'Exploitation de la Mer (IFREMER)-Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM), Laboratoire des Sciences de l'Environnement Marin (LEMAR) (LEMAR), Institut de Recherche pour le Développement (IRD)-Institut Français de Recherche pour l'Exploitation de la Mer (IFREMER)-Université de Brest (UBO)-Institut Universitaire Européen de la Mer (IUEM), Institut de Recherche pour le Développement (IRD)-Institut national des sciences de l'Univers (INSU - CNRS)-Université de Brest (UBO)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Institut national des sciences de l'Univers (INSU - CNRS)-Université de Brest (UBO)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), Alfred Wegener Institute for Polar and Marine Research (AWI), The is study was supported by the AWI-MARUM-IFREMER AMI Partnership Programme (DEADLY TRIO project), LabexMer (ANR-10LABX-0019, OASYS project), the Ministry of Ecological and Solidarity Transition and the Foundation for Biodiversity Research (Ocean Acidification Program, PACIO project), the Deutsche Forschungsgemeinschaft, PE 1157/8–1, MA4271/3–1 (the FITNESS project) and France Génomique National infrastructure, funded as part of 'Investissement d’Avenir' program managed by Agence Nationale pour la Recherche (contract ANR-10-INBS-09). Open Access funding enabled and organized by Projekt DEAL., ANR-10-INBS-0009,France-Génomique,Organisation et montée en puissance d'une Infrastructure Nationale de Génomique(2010), and ANR-10-LABX-0019,LabexMER,LabexMER Marine Excellence Research: a changing ocean(2010)
Subjects: Oceans and Seas, Neuro-sensory system, [SDE.MCG]Environmental Sciences/Global Changes, Betanodavirus, carbon-dioxide, Olfactory Mucosa, interferon-stimulated genes, Genetics, Animals, Homeostasis, Climate change, Anti-viral immunity, Seawater, mhc class-i, European sea bass, Transcriptomics, nod-like receptor, teleost fish, double-stranded-rna, Olfactory epithelium, Carbon Dioxide, Hydrogen-Ion Concentration, Long-term transgenerational ocean acidification, Metabolism, immune-response, Bass, reared sea-bass, [SDE.BE]Environmental Sciences/Biodiversity and Ecology, Transcriptome, mass mortalities, induced mx proteins, Biotechnology
Abstract: Background Progressive CO2-induced ocean acidification (OA) impacts marine life in ways that are difficult to predict but are likely to become exacerbated over generations. Although marine fishes can balance acid–base homeostasis efficiently, indirect ionic regulation that alter neurosensory systems can result in behavioural abnormalities. In marine invertebrates, OA can also affect immune system function, but whether this is the case in marine fishes is not fully understood. Farmed fish are highly susceptible to disease outbreak, yet strategies for overcoming such threats in the wake of OA are wanting. Here, we exposed two generations of the European sea bass (Dicentrarchus labrax) to end-of-century predicted pH levels (IPCC RCP8.5), with parents (F1) being exposed for four years and their offspring (F2) for 18 months. Our design included a transcriptomic analysis of the olfactory rosette (collected from the F2) and a viral challenge (exposing F2 to betanodavirus) where we assessed survival rates. Results We discovered transcriptomic trade-offs in both sensory and immune systems after long-term transgenerational exposure to OA. Specifically, RNA-Seq analysis of the olfactory rosette, the peripheral olfactory organ, from 18-months-old F2 revealed extensive regulation in genes involved in ion transport and neuronal signalling, including GABAergic signalling. We also detected OA-induced up-regulation of genes associated with odour transduction, synaptic plasticity, neuron excitability and wiring and down-regulation of genes involved in energy metabolism. Furthermore, OA-exposure induced up-regulation of genes involved in innate antiviral immunity (pathogen recognition receptors and interferon-stimulated genes) in combination with down-regulation of the protein biosynthetic machinery. Consistently, OA-exposed F2 challenged with betanodavirus, which causes damage to the nervous system of marine fish, had acquired improved resistance. Conclusion F2 exposed to long-term transgenerational OA acclimation showed superior viral resistance, though as their metabolic and odour transduction programs were altered, odour-mediated behaviours might be consequently impacted. Although it is difficult to unveil how long-term OA impacts propagated between generations, our results reveal that, across generations, trade-offs in plastic responses is a core feature of the olfactory epithelium transcriptome in OA-exposed F2 offspring, and will have important consequences for how cultured and wild fish interacts with its environment.
Published: 2022
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36. Core-, pan- and accessory genome analyses of Clostridium neonatale: insights into genetic diversity

Author: Victoria Mesa, Marc Monot, Laurent Ferraris, Michel Popoff, Christelle Mazuet, Frederic Barbut, Johanne Delannoy, Bruno Dupuy, Marie-Jose Butel, Julio Aires, Université Paris Cité (UPCité), Biomics (plateforme technologique), Institut Pasteur [Paris] (IP), Pathogénèse des Bactéries Anaérobies / Pathogenesis of Bacterial Anaerobes (PBA (U-Pasteur_6)), Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Centre National de Référence des Bactéries Anaérobies et Botulisme - National Reference Center Anaerobic Bacteria and Botulism (CNR), Institut Pasteur [Paris] (IP)-Université Paris Cité (UPCité), CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), This project was supported by a grant from l’Agence National pour la Recherche (ANR-13-PRTS-0018). The Biomics Platform is supported by France Génomique (ANR-10-INBS-09) and IBISA., ANR-13-PRTS-0018,ClosNEC,Clostridium et physiopathologie de l'entérocolite ulcéronécrosante du prématuré: approches clinique et moléculaire(2013), and ANR-10-INBS-0009,France-Génomique,Organisation et montée en puissance d'une Infrastructure Nationale de Génomique(2010)
Subjects: necrotizing enterocolitis, core-genome, closed genome, [SDV.BBM.BM]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, comparative genomics, pan-genome, General Medicine, [INFO.INFO-BI]Computer Science [cs]/Bioinformatics [q-bio.QM], [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, Clostridium neonatale
Abstract: Clostridium neonatale is a potential opportunistic pathogen recovered from faecal samples in cases of necrotizing enterocolitis (NEC), a gastrointestinal disease affecting preterm neonates. Although the C. neonatale species description and name validation were published in 2018, comparative genomics are lacking. In the present study, we provide the closed genome assembly of the C. neonatale ATCC BAA-265T (=250.09) reference strain with a manually curated functional annotation of the coding sequences. Pan-, core- and accessory genome analyses were performed using the complete 250.09 genome (4.7 Mb), three new assemblies (4.6–5.6 Mb), and five publicly available draft genome assemblies (4.6–4.7 Mb). The C. neonatale pan-genome contains 6840 genes, while the core-genome has 3387 genes. Pan-genome analysis revealed an ‘open’ state and genomic diversity. The strain-specific gene families ranged from five to 742 genes. Multiple mobile genetic elements were predicted, including a total of 201 genomic islands, 13 insertion sequence families, one CRISPR-Cas type I-B system and 15 predicted intact prophage signatures. Primary virulence classes including offensive, defensive, regulation of virulence-associated genes and non-specific virulence factors were identified. The presence of a tet(W/N/W) gene encoding a tetracycline resistance ribosomal protection protein and a 23S rRNA methyltransferase ermQ gene were identified in two different strains. Together, our results revealed a genetic diversity and plasticity of C. neonatale genomes and provide a comprehensive view of this species genomic features, paving the way for the characterization of its biological capabilities.
Published: 2022
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37. The seventh pandemic of cholera in Europe revisited by microbial genomics

Author: Radu Cojocaru, Anatoly N. Kravetz, Daniela Cristea, Jean Rauzier, Clifford G. Clark, Olivier Gascuel, Marie-Laure Quilici, François-Xavier Weill, Elisabeth Njamkepo, Adriana Simona Ciontea, Monakhova Ev, Maria Damian, Mihaela Oprea, Anna Zhukova, Cantacuzino National Medico-Military Institute for Research Development [Bucharest], Cantacuzino Institute [Romania], Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP), Bactéries pathogènes entériques (BPE), Institut Pasteur [Paris] (IP), Bioinformatique évolutive - Evolutionary Bioinformatics, Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Hub Bioinformatique et Biostatistique - Bioinformatics and Biostatistics HUB, National Microbiology Laboratory [Winnipeg, Canada], Public Health Agency of Canada, Kiev Research Institute of Epidemiology and Infectious Diseases, Rostov-on-Don Research Institute for Plague Control, National Centre for Public Health [Chisinau, Republic of Moldova], This study was supported by the Institut Pasteur, Cantacuzino NMMIRD, Santé publiqueFrance, the Fondation Le Roch-Les Mousquetaires, the French government’s Investisse-ment d’Avenir programme, Laboratoire d’Excellence‘Integrative Biology of EmergingInfectious Diseases’(grant number ANR-10-LABX-62-IBEID), and'Institut Convergence for the study of Emergence of Pathology Through Individuals and Populations'(INCEPTION, grant number PIA/ANR-16-CONV-0005). D.C. was supported by a trai-neeship grant from the Calmette and Yersin Program of the Institut Pasteur InternationalNetwork. M.O. was supported by a mobility grant from the Romanian Ministry of Research and Innovation CNCS - UEFISCDI, project no. 495/2018, within PNCDI III.The Institut Pasteur Biomics platform is supported by France Génomique (ANR10-INBS-09-08) and IBISA. We thank I. Najjar and L. Lemée for sequencing the isolates., ANR-10-LABX-0062,IBEID,Integrative Biology of Emerging Infectious Diseases(2010), ANR-16-CONV-0005,INCEPTION,Institut Convergences pour l'étude de l'Emergence des Pathologies au Travers des Individus et des populatiONs(2016), ANR-10-INBS-0009,France-Génomique,Organisation et montée en puissance d'une Infrastructure Nationale de Génomique(2010), Institut Pasteur [Paris], and Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS)
Subjects: 0301 basic medicine, Epidemiology, Black sea region, General Physics and Astronomy, MESH: Genome, Bacterial, Ribotyping, El Tor, West africa, Cholera, Pandemic, Socioeconomics, MESH: Phylogeny, lcsh:Science, Vibrio cholerae, Phylogeny, MESH: Evolution, Molecular, Multidisciplinary, Middle East, biology, MESH: Genomics, Genomics, 3. Good health, Europe, Geography, MESH: Human Migration, MESH: History, 20th Century, Pathogens, MESH: History, 21st Century, MESH: Pandemics, Science, Human Migration, 030106 microbiology, History, 21st Century, Article, General Biochemistry, Genetics and Molecular Biology, Evolution, Molecular, 03 medical and health sciences, Spatio-Temporal Analysis, MESH: Spatio-Temporal Analysis, MESH: Cholera, Drug Resistance, Bacterial, MESH: Drug Resistance, Bacterial, medicine, Humans, Clinical microbiology, Pandemics, MESH: Humans, Outbreak, MESH: Ribotyping, General Chemistry, History, 20th Century, medicine.disease, biology.organism_classification, Microbial genomics, Bacterial genes, 030104 developmental biology, lcsh:Q, MESH: Europe, [INFO.INFO-BI]Computer Science [cs]/Bioinformatics [q-bio.QM], Genome, Bacterial, MESH: Vibrio cholerae
Abstract: In 1970, the seventh pandemic of cholera (7 P) reached both Africa and Europe. Between 1970 and 2011, several European countries reported cholera outbreaks of a few to more than 2,000 cases. We report here a whole-genome analysis of 1,324 7 P V. cholerae El Tor (7 PET) isolates, including 172 from autochthonous sporadic or outbreak cholera cases occurring between 1970 and 2011 in Europe, providing insight into the spatial and temporal spread of this pathogen across Europe. In this work, we show that the 7 PET lineage was introduced at least eight times into two main regions: Eastern and Southern Europe. Greater recurrence of the disease was observed in Eastern Europe, where it persisted until 2011. It was introduced into this region from Southern Asia, often circulating regionally in the countries bordering the Black Sea, and in the Middle East before reaching Eastern Africa on several occasions. In Southern Europe, the disease was mostly seen in individual countries during the 1970s and was imported from North and West Africa, except in 1994, when cholera was imported into Albania and Italy from the Black Sea region. These results shed light on the geographic course of cholera during the seventh pandemic and highlight the role of humans in its global dissemination., Since 1970, several cholera outbreaks caused by the “seventh pandemic” (7PET) lineage have been reported in Europe. Here, the authors demonstrate that the outbreaks were caused by repeated introductions of 7PET into Europe, rather than local environmental sources.
Published: 2020
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38. High-throughput single-cell activity-based screening and sequencing of antibodies using droplet microfluidics

Author: Andrew D. Griffiths, Alexei Godina, Guillaume Mottet, Gaël A. Millot, Bingqing Shen, Samantha N. Stewart, Vera Menrath, Sosthene Essono, Baptiste Saudemont, Clément Nizak, Annabelle Gérard, Antoine Sautel-Caillé, Scott McNamara, Matthieu Delince, Sami Ellouze, Jean Baudry, Marcel Reichen, Pablo Canales-Herrerias, Charina Ortega, Patrick England, Carlos Castrillon, Odile Richard-Le Goff, Colin Brenan, Klaus Eyer, Pascaline Mary, Luis Briseño-Roa, Allan Jensen, Pierre Bruhns, Raphael Clement Li-Ming Doineau, Adam Woolfe, Roshan Kumar, Bin Jia, Bruno Iannascoli, Yannick Pousse, Kevin Grosselin, Gregory Rose, Adeline Poitou, HiFiBiO Therapeutics SAS [Paris], Anticorps en thérapie et pathologie - Antibodies in Therapy and Pathology, Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM), Ecole Doctorale Frontières du Vivant - Programme Bettencourt (FdV), Université Paris Descartes - Paris 5 (UPD5)-PRES Sorbonne Paris Cité, Chimie-Biologie-Innovation (UMR 8231) (CBI), Ecole Superieure de Physique et de Chimie Industrielles de la Ville de Paris (ESPCI Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Laboratoire Colloïdes et Matériaux Divisés (LCMD), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Centre National de la Recherche Scientifique (CNRS), HiFiBiO Therapeutics Inc. [Cambridge], Abbvie Bioresearch Center [Worcester], Hub Bioinformatique et Biostatistique - Bioinformatics and Biostatistics HUB, Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Biophysique Moléculaire (Plate-forme), Biophysique des macromolécules et leurs interactions, This work was supported by the French Agence Nationale de la Recherche (ANR-14-CE16-0011 project DROPmAbs), by the Centre d’Innovation et Recherche Technologique (Citech) through the Institut Carnot Pasteur Microbes & Santé (ANR 16 CARN 0023-01), by BPI France (OSIRIS and CELLIGO projects) and by the French ‘Investissements d’Avenir’ program via the CELLIGO project and grant agreements ANR-10-NANO-02, ANR-10-IDEX-0001-02 PSL, ANR-10-LABX-31 and ANR-10-EQPX-34. NGS was performed by the ICGex NGS platform of the Institut Curie and the Institut de Biologie Intégrative de la Cellule (I2BC) platform (Gif-sur-Yvette) supported by the grants ANR-10-EQPX-03 and ANR-10-INBS-09-08 (France Génomique Consortium), by the Canceropole Ile-de-France and by the SiRIC-Curie program (SiRIC Grant INCa-DGOS- 4654). C.C. acknowledges financial support from CONCYTEC, Peru. P.C.H. is a scholar in the Pasteur - Paris University (PPU) International PhD program and was also supported by the Fondation pour la Recherche Médicale (FRM, FDT201904008240). K.E. acknowledges financial support from the Swiss National Science Foundation and The Branco Weiss Fellowship - Society in Science., We would like to thank M. Holsti and W. Somers (Pfizer, BioMedicine Design) for advice on the technology development and critical reading of the manuscript, R. Nicol (Whitehead Institute, MIT Center for Genome Research) for advice on barcoded sequencing, at the Institut Pasteur, H. Mouquet for advice on antibody sequence selection, and F. Jönsson for advice on flow cytometry analysis, T. Kirk and S. Foulon (ESPCI Paris) for their help developing the barcoded hydrogel beads, S. N. Stewart (HiFiBio Therapeutics Inc.) for her help producing and analysing recombinant antibodies, the Institut Pierre-Gilles de Gennes (IPGG) for use of clean room facilities and the laser engraver (CII08, Axyslaser)., ANR-14-CE16-0011,DROP-mAbs,Analyse en profondeur de répertoires d'anticorps par microfluidique en gouttelettes couplé à du séquençage haut-débit pour le diagnostic et la découverte d'anticorps thérapeutiques(2014), ANR-10-IDEX-0001,PSL,Paris Sciences et Lettres(2010), ANR-10-EQPX-0034,IPGG,Institut Pierre Gilles de Gennes pour la microfluidique(2010), ANR-10-EQPX-0003,ICGex,Equipement de biologie intégrative du cancer pour une médecine personnalisée(2010), ANR-10-INBS-0009,France-Génomique,Organisation et montée en puissance d'une Infrastructure Nationale de Génomique(2010), Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Ecole Superieure de Physique et de Chimie Industrielles de la Ville de Paris (ESPCI Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL), Centre National de la Recherche Scientifique (CNRS)-Ecole Superieure de Physique et de Chimie Industrielles de la Ville de Paris (ESPCI Paris), Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Bruhns, Pierre, Appel à projets générique - Analyse en profondeur de répertoires d'anticorps par microfluidique en gouttelettes couplé à du séquençage haut-débit pour le diagnostic et la découverte d'anticorps thérapeutiques - - DROP-mAbs2014 - ANR-14-CE16-0011 - Appel à projets générique - VALID, Initiative d'excellence - Paris Sciences et Lettres - - PSL2010 - ANR-10-IDEX-0001 - IDEX - VALID, Equipements d'excellence - Institut Pierre Gilles de Gennes pour la microfluidique - - IPGG2010 - ANR-10-EQPX-0034 - EQPX - VALID, Equipements d'excellence - Equipement de biologie intégrative du cancer pour une médecine personnalisée - - ICGex2010 - ANR-10-EQPX-0003 - EQPX - VALID, and Organisation et montée en puissance d'une Infrastructure Nationale de Génomique - - France-Génomique2010 - ANR-10-INBS-0009 - INBS - VALID
Subjects: [SDV.IMM] Life Sciences [q-bio]/Immunology, Biomedical Engineering, Somatic hypermutation, Bioengineering, Cancer Vaccines, Applied Microbiology and Biotechnology, Antibodies, Mice, 03 medical and health sciences, 0302 clinical medicine, Antibody Repertoire, Antigen, Animals, Humans, Antigens, 030304 developmental biology, chemistry.chemical_classification, B-Lymphocytes, 0303 health sciences, biology, High-Throughput Nucleotide Sequencing, DNA, Microfluidic Analytical Techniques, Molecular biology, Reverse transcriptase, 3. Good health, Enzyme, chemistry, Immunization, Immunoglobulin G, biology.protein, [SDV.IMM]Life Sciences [q-bio]/Immunology, Molecular Medicine, Single-Cell Analysis, Antibody, 030217 neurology & neurosurgery, Ex vivo, Biotechnology
Abstract: International audience; Mining the antibody repertoire of plasma cells and plasmablasts could enable the discovery of useful antibodies for therapeutic or research purposes1. We present a method for high-throughput, single-cell screening of IgG-secreting primary cells to characterize antibody binding to soluble and membrane-bound antigens. CelliGO is a droplet microfluidics system that combines high-throughput screening for IgG activity, using fluorescence-based in-droplet single-cell bioassays2, with sequencing of paired antibody V genes, using in-droplet single-cell barcoded reverse transcription. We analyzed IgG repertoire diversity, clonal expansion and somatic hypermutation in cells from mice immunized with a vaccine target, a multifunctional enzyme or a membrane-bound cancer target. Immunization with these antigens yielded 100–1,000 IgG sequences per mouse. We generated 77 recombinant antibodies from the identified sequences and found that 93% recognized the soluble antigen and 14% the membrane antigen. The platform also allowed recovery of ~450–900 IgG sequences from ~2,200 IgG-secreting activated human memory B cells, activated ex vivo, demonstrating its versatility.
Published: 2020
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39. Bat coronaviruses related to SARS-CoV-2 and infectious for human cells

Author: Sarah Temmam, Khamsing Vongphayloth, Eduard Baquero, Sandie Munier, Massimiliano Bonomi, Béatrice Regnault, Bounsavane Douangboubpha, Yasaman Karami, Delphine Chrétien, Daosavanh Sanamxay, Vilakhan Xayaphet, Phetphoumin Paphaphanh, Vincent Lacoste, Somphavanh Somlor, Khaithong Lakeomany, Nothasin Phommavanh, Philippe Pérot, Océane Dehan, Faustine Amara, Flora Donati, Thomas Bigot, Michael Nilges, Félix A. Rey, Sylvie van der Werf, Paul T. Brey, Marc Eloit, Découverte de pathogènes – Pathogen discovery, Institut Pasteur [Paris] (IP)-Université Paris Cité (UPCité), Centre Collaborateur de l'OIE de Détection et identification chez l’homme des pathogènes animaux émergents et développement d’outils pour leur diagnostic / Collaborating Center for the Detection and identification in humans of emerging animal pathogens and development of tools for their diagnoses (CCOIE-OIECC), Institut Pasteur [Paris] (IP)-Organisation Mondiale de la Santé Animale / World Organisation Animal Health [Paris] (OIE)-Université Paris Cité (UPCité), Institut Pasteur du Laos, Réseau International des Instituts Pasteur (RIIP), Virologie Structurale - Structural Virology, Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Génétique Moléculaire des Virus à ARN - Molecular Genetics of RNA Viruses (GMV-ARN (UMR_3569 / U-Pasteur_2)), Bioinformatique structurale - Structural Bioinformatics, National University of Laos, Centre National de Référence des virus des infections respiratoires (dont la grippe) - National Reference Center Virus Influenzae [Paris] (CNR - laboratoire coordonnateur), Hub Bioinformatique et Biostatistique - Bioinformatics and Biostatistics HUB, École nationale vétérinaire - Alfort (ENVA), NGS was performed with the help of the Biomics Platform, Center for Technological Resources and Research, Institut Pasteur, Paris, France, supported by France Génomique (ANR-10-INBS-09-09), Inclusive Blockchain Insurance using Space Assets and the Illumina COVID-19 Projects’ offer. The work was granted access to the High Performance Computing resources of the Institute for Development and Resources in Intensive Scientific Computing under the allocation 2020-101592 made by Grand Équipement National de Calcul Intensif. We thank the Ministry of Health and the Ministry of Natural Resources and Environments, Lao People’s Democratic Republic, for their authorization of the field work and the Faculty of Environmental Science for its authorization of the field research collaboration. The work was supported by an Institut Pasteur 'Covid Taskforce' and in part by the H2020 project 101003589 (RECOVER) and Labex IBEID (ANR-10-LABX62-IBEID) grants. Field and laboratory work at IPL was also supported by a UK embassy grant (grant no. INT 2021/LOV C19 02) and a Luxembourg Development special grant (grant no. LAO/030·202324)., We thank S. Mohamed Ali, N. Da Rocha, A. Brisebarre, T. Xaybounsou and S. Chonephetsarath for their help at the bench, A. Haouz and the staff of the protein crystallogenesis facility at Institut Pasteur for help with crystallization trials, P. England from the Molecular Biophysics facility at Institut Pasteur for his support and access to the BLI equipment, P. Legrand from the PX1 beamline at Synchrotron SOLEIL for data collection support, and P. Guardado-Calvo for discussion and support with BLI experiments., ANR-10-LABX-0062,IBEID,Integrative Biology of Emerging Infectious Diseases(2010), ANR-10-INBS-0009,France-Génomique,Organisation et montée en puissance d'une Infrastructure Nationale de Génomique(2010), and European Project: 101003589, H2020-SC1-PHE-CORONAVIRUS-2020,RECOVER(2020)
Subjects: Asia, viruses, MESH: Spike Glycoprotein, Coronavirus, MESH: Angiotensin-Converting Enzyme 2, Chiroptera, Animals, Humans, MESH: Protein Binding, MESH: COVID-19, MESH: Animals, MESH: SARS-CoV-2, skin and connective tissue diseases, Taxonomy, Disease Reservoirs, MESH: Disease Reservoirs, Multidisciplinary, MESH: Humans, SARS-CoV-2, MESH: Asia, [SDV.BID.EVO]Life Sciences [q-bio]/Biodiversity/Populations and Evolution [q-bio.PE], fungi, COVID-19, MESH: Chiroptera, Biodiversity, body regions, Caves, Spike Glycoprotein, Coronavirus, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, MESH: Caves, Angiotensin-Converting Enzyme 2, Protein Binding
Abstract: International audience; The animal reservoir of SARS-CoV-2 is unknown despite reports of SARS-CoV-2-related viruses in Asian Rhinolophus bats1-4, including the closest virus from R. affinis, RaTG13 (refs. 5,6), and pangolins7-9. SARS-CoV-2 has a mosaic genome, to which different progenitors contribute. The spike sequence determines the binding affinity and accessibility of its receptor-binding domain to the cellular angiotensin-converting enzyme 2 (ACE2) receptor and is responsible for host range10-12. SARS-CoV-2 progenitor bat viruses genetically close to SARS-CoV-2 and able to enter human cells through a human ACE2 (hACE2) pathway have not yet been identified, although they would be key in understanding the origin of the epidemic. Here we show that such viruses circulate in cave bats living in the limestone karstic terrain in northern Laos, in the Indochinese peninsula. We found that the receptor-binding domains of these viruses differ from that of SARS-CoV-2 by only one or two residues at the interface with ACE2, bind more efficiently to the hACE2 protein than that of the SARS-CoV-2 strain isolated in Wuhan from early human cases, and mediate hACE2-dependent entry and replication in human cells, which is inhibited by antibodies that neutralize SARS-CoV-2. None of these bat viruses contains a furin cleavage site in the spike protein. Our findings therefore indicate that bat-borne SARS-CoV-2-like viruses that are potentially infectious for humans circulate in Rhinolophus spp. in the Indochinese peninsula.
Published: 2022
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40. The gut environment regulates bacterial gene expression which modulates susceptibility to bacteriophage infection

Author: Marta Lourenço, Lorenzo Chaffringeon, Quentin Lamy-Besnier, Marie Titécat, Thierry Pédron, Odile Sismeiro, Rachel Legendre, Hugo Varet, Jean-Yves Coppée, Marion Bérard, Luisa De Sordi, Laurent Debarbieux, Bactériophage, bactérie, hôte - Bacteriophage, bacterium, host, Université Paris Cité (UPCité)-Microbiologie Intégrative et Moléculaire (UMR6047), Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Collège Doctoral, Sorbonne Université (SU), Centre de Recherche Saint-Antoine (CRSA), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Paris Center for Microbiome Medicine (FHU PaCeMM), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Institute for Translational Research in Inflammation - U 1286 (INFINITE (Ex-Liric)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Biomics (plateforme technologique), Institut Pasteur [Paris] (IP)-Université Paris Cité (UPCité), Transcriptome et Epigénome (PF2), Institut Pasteur [Paris] (IP), Hub Bioinformatique et Biostatistique - Bioinformatics and Biostatistics HUB, Animalerie Centrale (plateforme) - Central Animal Facility (platform) (C2RA), M.L. is funded as part of the Pasteur-Paris University (PPU) International PhD Program. M.L. is funded by Institut Carnot Pasteur Maladies Infectieuses (ANR 11-CARN 017-01). L.D.S. is funded by a Roux-Cantarini Fellowship from the Institut Pasteur (Paris, France). L.C. is funded by a PhD Fellowship from the Ministère de l’Enseignement Supérieur et de la Recherche, France, École Doctorale 394. Q.L.-B. is funded by École Doctorale FIRE - Programme Bettencourt. M.T. received a fellowship from Fondation DigestScience (Lille, France). The transcriptome and epigenome Platform is part of the France Génomique consortium (ANR10-NBS-09-08)., We thank Jorge Moura de Sousa for writing the customized R script for the pairwise comparisons between lists of genes from the different samples and for critically reading the manuscript. We thank Dwayne Roach and Anne Chevallereau for valuable discussions. We thank the Genetics of Biofilms team (Jean-Marc Ghigo) of Institut Pasteur and in particular Anne-Aurélie Lopes for training on the biofilm assays and Christophe Beloin for access to the ASKA plasmids collection. We thank the members of the Centre for Gnotobiology Platform of the Institut Pasteur (Thierry Angélique, Eddie Maranghi, Martine Jacob, Jérome Toutain, and Marisa Gabriela Lopez Dieguez) for their help with the animal work., ANR-10-INBS-0009,France-Génomique,Organisation et montée en puissance d'une Infrastructure Nationale de Génomique(2010), Varet, Hugo, and Organisation et montée en puissance d'une Infrastructure Nationale de Génomique - - France-Génomique2010 - ANR-10-INBS-0009 - INBS - VALID
Subjects: intestinal microbiota, MESH: Gene Expression, [SDV]Life Sciences [q-bio], Gene Expression, enteric pathogens, Microbiology, auto-inducer, flagellum, Mice, transcriptomics, Virology, Escherichia coli, Animals, Bacteriophages, MESH: Animals, MESH: Bacteriophages, MESH: Mice, Bacteria, MESH: Escherichia coli, lipopolysaccharide, [SDV] Life Sciences [q-bio], MESH: Bacteria, motility, Genes, Bacterial, Parasitology, biofilms, MESH: Genes, Bacterial, gene regulation
Abstract: International audience; Abundance and diversity of bacteria and their viral predators, bacteriophages (phages), in the digestive tract are associated with human health. Particularly intriguing is the long-term coexistence of these two antagonistic populations. We performed genome-wide RNA sequencing on a human enteroaggregative Escherichia coli isolate to identify genes differentially expressed between in vitro conditions and in murine intestines. We experimentally demonstrated that four of these differentially expressed genes modified the interactions between E. coli and three virulent phages by either increasing or decreasing its susceptibility/resistance pattern and also by interfering with biofilm formation. Therefore, the regulation of bacterial genes expression during the colonization of the digestive tract influences the coexistence of phages and bacteria, highlighting the intricacy of tripartite relationships between phages, bacteria, and the animal host in intestinal homeostasis.
Published: 2022
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41. ePeak: from replicated chromatin profiling data to epigenomic dynamics

Author: Maëlle Daunesse, Rachel Legendre, Hugo Varet, Adrien Pain, Claudia Chica, Hub Bioinformatique et Biostatistique - Bioinformatics and Biostatistics HUB, Institut Pasteur [Paris] (IP)-Université Paris Cité (UPCité), European Bioinformatics Institute [Cambridge, UK], Biomics (plateforme technologique), Biomics Platform of the Institut Pasteur is supported by France Génomique [ANR-10-INBS-09-09], IBiSA., Authors would like to thank Victoire Baillet for help in code debugging and critical reading of the manuscript, Thomas Bigot and Blaise Li for advice on the Snakemake development and the singularity packaging, Julien Guglielmini for guidance on Bash and all members of the Hub of Bioinformatics and Biostatistics for useful discussions. This work used the computational and storage services (MAESTRO cluster) provided by the IT department at Institut Pasteur, Paris, and the Core Cluster of the Institut Français de Bioinformatique (IFB) (ANR-11-INBS-0013)., and ANR-10-INBS-0009,France-Génomique,Organisation et montée en puissance d'une Infrastructure Nationale de Génomique(2010)
Subjects: [SDV]Life Sciences [q-bio], General Medicine
Abstract: We present ePeak, a Snakemake-based pipeline for the identification and quantification of reproducible peaks from raw ChIP-seq, CUT&RUN and CUT&Tag epigenomic profiling techniques. It also includes a statistical module to perform tailored differential marking and binding analysis with state of the art methods. ePeak streamlines critical steps like the quality assessment of the immunoprecipitation, spike-in calibration and the selection of reproducible peaks between replicates for both narrow and broad peaks. It generates complete reports for data quality control assessment and optimal interpretation of the results. We advocate for a differential analysis that accounts for the biological dynamics of each chromatin factor. Thus, ePeak provides linear and nonlinear methods for normalisation as well as conservative and stringent models for variance estimation and significance testing of the observed marking/binding differences. Using a published ChIP-seq dataset, we show that distinct populations of differentially marked/bound peaks can be identified. We study their dynamics in terms of read coverage and summit position, as well as the expression of the neighbouring genes. We propose that ePeak can be used to measure the richness of the epigenomic landscape underlying a biological process by identifying diverse regulatory regimes.
Published: 2022
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42. Epitope convergence of broadly HIV-1 neutralizing IgA and IgG antibody lineages in a viremic controller

Author: Valérie Lorin, Ignacio Fernández, Guillemette Masse-Ranson, Mélanie Bouvin-Pley, Luis M. Molinos-Albert, Cyril Planchais, Thierry Hieu, Gérard Péhau-Arnaudet, Dominik Hrebík, Giulia Girelli-Zubani, Oriane Fiquet, Florence Guivel-Benhassine, Rogier W. Sanders, Bruce D. Walker, Olivier Schwartz, Johannes F. Scheid, Jordan D. Dimitrov, Pavel Plevka, Martine Braibant, Michael S. Seaman, François Bontems, James P. Di Santo, Félix A. Rey, Hugo Mouquet, Immunologie humorale - Humoral Immunology, Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Virologie Structurale, Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Immunité Innée - Innate Immunity, Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM), Morphogénèse et antigénicité du VIH et du virus des Hépatites (MAVIVH - U1259 Inserm - CHRU Tours ), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-Université de Tours (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM), Imagopole (CITECH), Institut Pasteur [Paris] (IP), Microscopie Ultrastructurale (Plate-forme), Masaryk University [Brno] (MUNI), Virus et Immunité - Virus and immunity (CNRS-UMR3569), University of Amsterdam [Amsterdam] (UvA), Weill Medical College of Cornell University [New York], Massachusetts General Hospital [Boston], Harvard Medical School [Boston] (HMS), Rockefeller University [New York], Centre de Recherche des Cordeliers (CRC (UMR_S_1138 / U1138)), École Pratique des Hautes Études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université Paris Cité (UPCité), Beth Israel Deaconess Medical Center [Boston] (BIDMC), Institut de Chimie des Substances Naturelles (ICSN), Institut de Chimie du CNRS (INC)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS), The NanoImaging Core was created with the help of a grant from the French Government’s Investissements d’Avenir program (EQUIPEX CACSICE - Centre d’analyse de systèmes complexes dans les environnements complexes, ANR-11-EQPX-0008). We thank the NIH AIDS Reagent Program (Division of AIDS, National Institute of Allergy and Infectious Diseases, NIH) for contributing to reagents and the Agence National de Recherche sur le SIDA et les hépatites virales (ANRS) for an equipment grant support. The Biomics platform is supported by France Génomique (ANR-10-INBS-09-09) and IBISA. I. Fernández and C. Planchais were recipients of an ANRS postdoctoral fellowship. The J.P. Di Santo laboratory received support from the Vaccine Research Institute (Créteil, France). H. Mouquet received core grants from the Institut Pasteur, Institut national de la santé et de la recherche médicale, and the Milieu Intérieur Program (ANR-10-LABX-69-01). This work was supported by the European Research Council Seventh Framework Program (ERC-2013-StG 337146), and by Gilead Sciences HIV Cure Grants (#00397)., ANR-11-EQPX-0008,CACSICE,Centre d'analyse de systèmes complexes dans les environnements complexes(2011), ANR-10-INBS-0009,France-Génomique,Organisation et montée en puissance d'une Infrastructure Nationale de Génomique(2010), ANR-10-LABX-0069,MILIEU INTERIEUR,GENETIC & ENVIRONMENTAL CONTROL OF IMMUNE PHENOTYPE VARIANCE: ESTABLISHING A PATH TOWARDS PERSONALIZED MEDICINE(2010), European Project: 337146,EC:FP7:ERC,ERC-2013-StG,HUMANTIVIRUSES(2014), Medical Microbiology and Infection Prevention, and AII - Infectious diseases
Subjects: Immunology, env Gene Products, Human Immunodeficiency Virus, HIV Infections, HIV Antibodies, Antibodies, Neutralizing, Immunoglobulin A, Epitopes, Mice, Polysaccharides, Immunoglobulin G, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, HIV-1, Immunology and Allergy, Animals, Humans, Elite Controllers, Broadly Neutralizing Antibodies
Abstract: International audience; Decrypting the B cell ontogeny of HIV-1 broadly neutralizing antibodies (bNAbs) is paramount for vaccine design. Here, we characterized IgA and IgG bNAbs of three distinct B cell lineages in a viremic controller, two of which comprised only IgG+ or IgA+ blood memory B cells; the third combined both IgG and IgA clonal variants. 7-269 bNAb in the IgA-only lineage displayed the highest neutralizing capacity despite limited somatic mutation, and delayed viral rebound in humanized mice. bNAbs in all three lineages targeted the N332 glycan supersite. The 2.8-Å resolution cryo-EM structure of 7-269-BG505 SOSIP.664 complex showed a similar pose as 2G12, on an epitope mainly composed of sugar residues comprising the N332 and N295 glycans. Binding and cryo-EM structural analyses showed that antibodies from the two other lineages interact mostly with glycans N332 and N386. Hence, multiple B cell lineages of IgG and IgA bNAbs focused on a unique HIV-1 site of vulnerability can codevelop in HIV-1 viremic controllers.
Published: 2022
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43. Bacteroides thetaiotaomicron uses a widespread extracellular DNase to promote bile-dependent biofilm formation

Author: Nathalie Béchon, Jovana Mihajlovic, Anne-Aurélie Lopes, Sol Vendrell-Fernández, Julien Deschamps, Romain Briandet, Odile Sismeiro, Isabelle Martin-Verstraete, Bruno Dupuy, Jean-Marc Ghigo, Génétique des Biofilms - Genetics of Biofilms, Université Paris Cité (UPCité)-Microbiologie Intégrative et Moléculaire (UMR6047), Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), AP-HP Hôpital universitaire Robert-Debré [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), MICrobiologie de l'ALImentation au Service de la Santé (MICALIS), AgroParisTech-Université Paris-Saclay-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Biomics (plateforme technologique), Institut Pasteur [Paris] (IP)-Université Paris Cité (UPCité), Pathogénèse des Bactéries Anaérobies / Pathogenesis of Bacterial Anaerobes (PBA (U-Pasteur_6)), Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Institut Universitaire de France (IUF), Ministère de l'Education nationale, de l’Enseignement supérieur et de la Recherche (M.E.N.E.S.R.), This work was supported by an Institut Pasteur grant and by the French government’s Investissement d’Avenir Program, Laboratoire d’Excellence 'Integrative Biology of Emerging Infectious Diseases' (Grant ANR-10-LABX-62-IBEID) and the Fondation pour la Recherche Médicale (Grant DEQ20180339185). N.B. was supported by a Ministère Français de l’Education Nationale, de l’Enseignement Supérieur et de la Recherche fellowship. J.M. was supported by the Pasteur Paris University International Doctoral Program and the Fondation pour la Recherche Médicale (Grant FDT20160435523). The RNA-seq experiments were performed by the Biomics Platform, C2RT, Institut Pasteur, Paris, France, supported by France Génomique (Grant ANR-10-INBS-09-09) and Infrastructures en Biologie Santé et Agronomie (IBISA)., ANR-10-LABX-0062,IBEID,Integrative Biology of Emerging Infectious Diseases(2010), and ANR-10-INBS-0009,France-Génomique,Organisation et montée en puissance d'une Infrastructure Nationale de Génomique(2010)
Subjects: carbohydrates (lipids), Bacteroides thetaiotaomicron, DNase, Multidisciplinary, fluids and secretions, gut microbiota, [SDV]Life Sciences [q-bio], bacteria, biochemical phenomena, metabolism, and nutrition, digestive system, biofilm
Abstract: Significance Biofilms are communities of surface-attached bacteria exhibiting biofilm-specific properties. Although anaerobic biofilms impact health, industry, and environment, they are mostly studied in aerobic bacterial species. Here, we studied biofilm formation in Bacteroides thetaiotaomicron , an anaerobic gut symbiont degrading diet sugars and contributing to gut maturation. Although B. thetaiotaomicron adhesion contributes to intestinal colonization, little is known about the determinants of its biofilm capacities. We identified that bile is a physiologically relevant gut signal inducing biofilm formation in B. thetaiotaomicron and other gut Bacteroidales. Moreover, we showed that, in contrast to the known scaffolding role of extracellular DNA, bile-dependent biofilm requires a DNase degrading matrix DNA, thus revealing a previously unrecognized factor contributing to the adhesion capacity of major gut symbionts.
Published: 2022
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44. RNA Sequencing Reveals Widespread Transcription of Natural Antisense RNAs in Entamoeba Species

Author: Damien Mornico, Chung-Chau Hon, Mikael Koutero, Christian Weber, Jean-Yves Coppée, C Graham Clark, Marie-Agnes Dillies, Nancy Guillen, Hub Bioinformatique et Biostatistique - Bioinformatics and Biostatistics HUB, Institut Pasteur [Paris] (IP)-Université Paris Cité (UPCité), Biologie Cellulaire du Parasitisme, Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM), Transcriptome et Epigénome (PF2), Institut Pasteur [Paris] (IP), London School of Hygiene and Tropical Medicine (LSHTM), Biologie des Interactions Hôte-Parasite - Biology of Host-Parasite Interactions, Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), The work was funded by the National French Research Agency (ANR- GENOM-BTV 2010-Grant GENM-0011-01, GENAMIBE). The Transcriptome and Epigenome Platform is a member of the France Génomique consortium (ANR10-NBS-09-08)., ANR-10-GENM-0011,GENAMIBE,Comprendre la pathogenicité de Entamoeba par l'utilisation de la transcriptomique et la phylogénétique comparatives(2010), ANR-10-INBS-0009,France-Génomique,Organisation et montée en puissance d'une Infrastructure Nationale de Génomique(2010), Mornico, Damien, Génomique, Biotechnologies végétales - Comprendre la pathogenicité de Entamoeba par l'utilisation de la transcriptomique et la phylogénétique comparatives - - GENAMIBE2010 - ANR-10-GENM-0011 - Génomique - VALID, and Organisation et montée en puissance d'une Infrastructure Nationale de Génomique - - France-Génomique2010 - ANR-10-INBS-0009 - INBS - VALID
Subjects: Microbiology (medical), transcriptomics, fluids and secretions, parasite, genomics, antisense RNA, Virology, [SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], parasitic diseases, [SDV.BBM.GTP] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], Microbiology, digestive system diseases
Abstract: International audience; Entamoeba is a genus of Amoebozoa that includes the intestine-colonizing pathogenic species Entamoeba histolytica. To understand the basis of gene regulation in E. histolytica from an evolutionary perspective, we have profiled the transcriptomes of its closely related species E. dispar, E. moshkovskii and E. invadens. Genome-wide identification of transcription start sites (TSS) and polyadenylation sites (PAS) revealed the similarities and differences of their gene regulatory sequences. In particular, we found the widespread initiation of antisense transcription from within the gene coding sequences is a common feature among all Entamoeba species. Interestingly, we observed the enrichment of antisense transcription in genes involved in several processes that are common to species infecting the human intestine, e.g., the metabolism of phospholipids. These results suggest a potentially conserved and compact gene regulatory system in Entamoeba.
Published: 2022
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45. The success of the bloom-forming cyanobacteria Planktothrix: Genotypes variability supports variable responses to light and temperature stress

Author: Sandra Kim Tiam, Katia Comte, Caroline Dalle, Marine Delagrange, Chakib Djediat, Bertrand Ducos, Charlotte Duval, Kathleen Feilke, Sahima Hamlaoui, Séverine Le Manach, Pierre Setif, Claude Yéprémian, Benjamin Marie, Diana Kirilovsky, Muriel Gugger, Cécile Bernard, Molécules de Communication et Adaptation des Micro-organismes (MCAM), Muséum national d'Histoire naturelle (MNHN)-Centre National de la Recherche Scientifique (CNRS), Collection des Cyanobactéries, Institut Pasteur [Paris] (IP)-Université Paris Cité (UPCité), Laboratoire de physique de l'ENS - ENS Paris (LPENS), Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité)-Département de Physique de l'ENS-PSL, École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL), ABCD : Biophysique des Biomolécules, Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité)-Département de Physique de l'ENS-PSL, CEA- Saclay (CEA), Commissariat à l'énergie atomique et aux énergies alternatives (CEA), This work was supported by the ANR CYPHER project, grant ANR-15-CE34–0002 of the French Agence Nationale de la Recherche. The collection Pasteur Culture of Cyanobacteria is funded by the Institut Pasteur. We acknowledged the LABGeM (CEA/Genoscope & CNRS UMR8030), the France Génomique and French Bioinformatics Institute national infrastructures (funded as part of Investissement d'Avenir program managed by Agence Nationale pour la Recherche, contracts ANR-10-INBS-09 and ANR-11-INBS-0013) are for support within the MicroScope annotation platform.' The mass spectrometry analyses were acquired at the Plateau technique de spectrométrie de masse bio-organique, Muséum National d'Histoire Naturelle, Paris, France., ANR-15-CE34-0002,CYPHER,Rôle cellulaire de toxines de cyanobactéries et réponses aux stress environementaux(2015), and ANR-11-INBS-0013,IFB (ex Renabi-IFB),Institut français de bioinformatique(2011)
Subjects: [SDV.EE.ECO]Life Sciences [q-bio]/Ecology, environment/Ecosystems, Planktothrix, Genotype, [SDV]Life Sciences [q-bio], [SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], Temperature, Humans, Plant Science, Aquatic Science, Cyanobacteria, Ecosystem
Abstract: International audience; Cyanobacterial blooms can modify the dynamic of aquatic ecosystems and have harmful consequences for human activities. Moreover, cyanobacteria can produce a variety of cyanotoxins, including microcystins, but little is known about the role of environmental factors on the prevalence of microcystin producers in the cyanobacterial bloom dynamics. This study aimed to better understand the success of Planktothrix in various environments by unveiling the variety of strategies governing cell responses to sudden changes in light intensity and temperature. The cellular responses (photosynthesis, photoprotection, heat shock response and metabolites synthesis) of four Planktothrix strains to highlight or high-temperature were studied, focusing on how distinct ecotypes (red-or green-pigmented) and microcystin production capability affect cyanobacteria's ability to cope with such abiotic stimuli. Our results showed that highlight and high-temperature impact different cellular processes and that Planktothrix responses are heterogeneous, specific to each strain and thus, to genotype. The ability of cyanobacteria to cope with sudden increase in light intensity and temperature was not related to red-or greenpigmented ecotype or microcystin production capability. According to our results, microcystin producers do not cope better to highlight or high-temperature and microcystin content does not increase in response to such stresses.
Published: 2022
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46. Sex in the city: Uncovering sex-specific management of equine resources from prehistoric times to the Modern Period in France

Author: Benoît Clavel, Sébastien Lepetz, Lorelei Chauvey, Stéphanie Schiavinato, Laure Tonasso-Calvière, Xuexue Liu, Antoine Fages, Naveed Khan, Andaine Seguin-Orlando, Clio Der Sarkissian, Pierre Clavel, Oscar Estrada, Duha Alioğlu, Charleen Gaunitz, Jean-Marc Aury, Maude Barme, Pierre Bodu, Monique Olive, Olivier Bignon-Lau, Jean-Christophe Castel, Myriam Boudadi-Maligne, Nicolas Boulbes, Alice Bourgois, Franck Decanter, Sylvain Foucras, Stéphane Frère, Armelle Gardeisen, Gaëtan Jouanin, Charlotte Méla, Nicolas Morand, Ariadna Nieto Espinet, Aude Perdereau, Olivier Putelat, Julie Rivière, Opale Robin, Marilyne Salin, Silvia Valenzuela-Lamas, Christian Vallet, Jean-Hervé Yvinec, Patrick Wincker, Ludovic Orlando, Ethnologie préhistorique, Archéologies et Sciences de l'Antiquité (ArScAn), Université Paris 1 Panthéon-Sorbonne (UP1)-Université Paris 8 Vincennes-Saint-Denis (UP8)-Université Paris Nanterre (UPN)-Ministère de la Culture et de la Communication (MCC)-Institut national de recherches archéologiques préventives (Inrap)-Centre National de la Recherche Scientifique (CNRS)-Université Paris 1 Panthéon-Sorbonne (UP1)-Université Paris 8 Vincennes-Saint-Denis (UP8)-Université Paris Nanterre (UPN)-Ministère de la Culture et de la Communication (MCC)-Institut national de recherches archéologiques préventives (Inrap)-Centre National de la Recherche Scientifique (CNRS), Technologie et Ethnologie des Mondes Préhistoriques (TEMPS), Université Paris 1 Panthéon-Sorbonne (UP1)-Université Paris Nanterre (UPN)-Centre National de la Recherche Scientifique (CNRS), Archéozoologie, archéobotanique : sociétés, pratiques et environnements (AASPE), Muséum national d'Histoire naturelle (MNHN)-Centre National de la Recherche Scientifique (CNRS), Centre d'anthropologie et de génomique de Toulouse (CAGT), Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Centre National de la Recherche Scientifique (CNRS), Génomique métabolique (UMR 8030), Genoscope - Centre national de séquençage [Evry] (GENOSCOPE), Université Paris-Saclay-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université d'Évry-Val-d'Essonne (UEVE)-Centre National de la Recherche Scientifique (CNRS), Centre de Recherche Archéologique de la Vallée de l'Oise (CRAVO), Muséum national d'Histoire naturelle (MNHN), Université Paris 1 Panthéon-Sorbonne (UP1)-Université Paris 8 Vincennes-Saint-Denis (UP8)-Université Paris Nanterre (UPN)-Ministère de la Culture et de la Communication (MCC)-Centre National de la Recherche Scientifique (CNRS), Université Paris 1 Panthéon-Sorbonne (UP1)-Université Paris 8 Vincennes-Saint-Denis (UP8)-Université Paris Nanterre (UPN)-Ministère de la Culture et de la Communication (MCC)-Centre National de la Recherche Scientifique (CNRS)-Université Paris 1 Panthéon-Sorbonne (UP1)-Université Paris 8 Vincennes-Saint-Denis (UP8)-Université Paris Nanterre (UPN)-Ministère de la Culture et de la Communication (MCC)-Centre National de la Recherche Scientifique (CNRS), Museum d'Histoire Naturelle [Genève] (MHN), De la Préhistoire à l'Actuel : Culture, Environnement et Anthropologie (PACEA), Université de Bordeaux (UB)-Centre National de la Recherche Scientifique (CNRS), Histoire naturelle de l'Homme préhistorique (HNHP), Muséum national d'Histoire naturelle (MNHN)-Université de Perpignan Via Domitia (UPVD)-Centre National de la Recherche Scientifique (CNRS), Institut national de recherches archéologiques préventives (Inrap), Archéologie et Archéométrie (ArAr), Université Lumière - Lyon 2 (UL2)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), Archéologie des Sociétés Méditerranéennes (ASM), Université Paul-Valéry - Montpellier 3 (UPVM)-Centre National de la Recherche Scientifique (CNRS)-Ministère de la Culture (MC), Direction Archéologie et Muséum de la ville d'Aix-en-Provence, Centre Technique Municipal RTE des Milles Aix-en-Provence, Institut Royal des Sciences Naturelles de Belgique (IRSNB), Archéologie et histoire ancienne : Méditerranée - Europe (ARCHIMEDE), Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Ministère de la Culture et de la Communication (MCC)-Centre National de la Recherche Scientifique (CNRS), Institución Milá y Fontanals de investigación en Humanidades (IMF), Consejo Superior de Investigaciones Científicas [Madrid] (CSIC), CEA- Saclay (CEA), Commissariat à l'énergie atomique et aux énergies alternatives (CEA), ANR-10-INBS-0009,France-Génomique,Organisation et montée en puissance d'une Infrastructure Nationale de Génomique(2010), ANR-17-EURE-0010,CHESS,Toulouse Graduate School défis en économie et sciences sociales quantitatives(2017), European Project: 681605,PEGASUS, Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS), Université Paris 1 Panthéon-Sorbonne (UP1)-Université Paris 8 Vincennes-Saint-Denis (UP8)-Université Paris Nanterre (UPN)-Ministère de la Culture et de la Communication (MCC)-Institut national de recherches archéologiques préventives (Inrap)-Centre National de la Recherche Scientifique (CNRS), Departamento de Arqueologı'a y Antropologı'a, Istitucio' Mila' i Fontanals, (IMF CSIC), Consejo Superior de Investigaciones Cientıficas (IMF-CSIC), Centre National de la Recherche Scientifique (France), European Research Council, France Génomique, Université de Toulouse, Villum Fonden, and Agence Nationale de la Recherche (France)
Subjects: Archeology, Ancient DNA, [SHS.ARCHEO]Humanities and Social Sciences/Archaeology and Prehistory, Iron age, City, Breeding, Horse, Middle ages, Roman period, [SHS]Humanities and Social Sciences, Donkey, [SDE]Environmental Sciences, Husbandry, Hunting, Mule, Archaeozoology
Abstract: Sex identification from fragmentary archeozoological assemblages is particularly challenging in the Equid family, including for horses, donkeys and their hybrids. This limitation has precluded in-depth investigations of sex-ratio variation in various temporal, geographic and social contexts. Recently, shallow DNA sequencing has offered an economical solution to equine sex determination, even in environments where DNA preservation conditions is not optimal. In this study, we applied state-of-the-art methods in ancient DNA-based equine sex determination to 897 osseous remains in order to assess whether equal proportions of males and females could be found in a range of archeological contexts in France. We found Magdalenian horse hunt not focused on isolated bachelors, and Upper Paleolithic habitats and natural traps equally balancing sex ratios. In contrast, Iron Age sacrificial rituals appeared to have been preferentially oriented to male horses and this practice extended into the Roman Period. During Antiquity, the Middle Ages and the Modern Period, cities emerged as environments largely dominated by horse males. This strong sex-bias was considerably reduced, and sometimes even absent, in various rural contexts. Combined with previous archaeozoological work and textual evidence, our results portray an urban economy fueled by adult, often old, males, and rural environments where females and subadults of both sexes were maintained to sustain production demands., We thank Agnès Orsoni, Michela Leonardi, and Stefanie Wagner for lab assistance and all members of the AGES research team at CAGT for fruitful discussions. We also thank all archaeologists, curators and staff in charge of archaeological warehouses, who have facilitated access to the material analyzed in this study. Pierre Clavel’s PhD position is funded by the CNRS MITI interdisciplinary programme (‘Mission pour les Initiatives Transverses et Interdisciplinaires’). Xuexue Liu was supported by the European Union’s Horizon 2020 research and Innovation pro- gramme under the Marie Skłodowska-Curie grant agreement 101027750. This work was supported by the France G ́enomique Appel `a Grand Projet (ANR-10-INBS-09-08, BUCEPHALE project); the Initiative d’Excellence Chaires d’attractivit ́e, Universit ́e de Toulouse (OURASI) and the Villum Fonden miGENEPI research project. Andaine Seguin- Orlando acknowledges IAST for funding from ANR (France) under grant ANR-17-EURE-0010 (‘Investissements d’Avenir’ programme). This project has received funding from the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation programme (grant agreement No. 681605).
Published: 2022
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47. FishmiRNA: An Evolutionarily Supported MicroRNA Annotation and Expression Database for Ray-Finned Fishes

Author: Thomas Desvignes, Philippe Bardou, Jérôme Montfort, Jason Sydes, Cervin Guyomar, Simon George, John H Postlethwait, Julien Bobe, Girard, Agnès, APPEL À PROJETS GÉNÉRIQUE 2018 - Elucider les bases cellulaires de la fécondité chez le poisson : dynamique et régulation de l'ovogenèse chez le medaka - - DynaMO2018 - ANR-18-CE20-0004 - AAPG2018 - VALID, Organisation et montée en puissance d'une Infrastructure Nationale de Génomique - - France-Génomique2010 - ANR-10-INBS-0009 - INBS - VALID, University of Oregon [Eugene], Système d'Information des GENomes des Animaux d'Elevage (SIGENAE), Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Laboratoire de Physiologie et Génomique des Poissons (LPGP), Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique )-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Institut de Génomique Fonctionnelle - Montpellier GenomiX (IGF MGX), Institut de Génomique Fonctionnelle (IGF), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM)-BioCampus (BCM), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), This work was supported by the National Institutes of Health (grant numbers NIH R24 OD011199, NIH 5R01 OD011116, and NIH R01 GM085318 to JHP), the National Science Foundation Office of Polar Program (NSF OPP-1543383 to JHP and TD), and the Agence Nationale de la Recherche (ANR-18-CE20-0004 to JB). This work benefited from access to the University of Oregon high performance computer, Talapas. MGX acknowledges financial support from France Génomique National infrastructure, funded as part of 'Investissement d'Avenir' program managed by Agence National pour la Recherche (ANR-10-INBS-09)., ANR-18-CE20-0004,DynaMO,Elucider les bases cellulaires de la fécondité chez le poisson : dynamique et régulation de l'ovogenèse chez le medaka(2018), and ANR-10-INBS-0009,France-Génomique,Organisation et montée en puissance d'une Infrastructure Nationale de Génomique(2010)
Subjects: [INFO.INFO-DB]Computer Science [cs]/Databases [cs.DB], Teleost, [SDV]Life Sciences [q-bio], non-coding RNA, Fishes, bowfin Amia calva, Holostei, [SDV] Life Sciences [q-bio], Whole Genome Duplication, MicroRNAs, actinopterygian, Genetics, [INFO.INFO-DB] Computer Science [cs]/Databases [cs.DB], Animals, Molecular Biology, Ecology, Evolution, Behavior and Systematics
Abstract: MicroRNAs (miRNAs) are important post-transcriptional regulators of gene expression involved in countless biological processes and are widely studied across metazoans. Although miRNA research continues to grow, the large community of fish miRNA researchers lacks exhaustive resources consistent among species. To fill this gap, we developed FishmiRNA, an evolutionarily supported miRNA annotation and expression database for ray-finned fishes: www.fishmirna.org. The self-explanatory database contains detailed, manually curated miRNA annotations with orthology relationships rigorously established by sequence similarity and conserved syntenies, and expression data provided for each detected mature miRNA. In just few clicks, users can download the annotation and expression database in several convenient formats either in its entirety or a subset. Simple filters and Blast search options also permit the simultaneous exploration and visual comparison of expression data for up to any ten mature miRNAs across species and organs. FishmiRNA was specifically designed for ease of use to reach a wide audience.
Published: 2022
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48. Competition Between Phage-Resistance Mechanisms Determines the Outcome of Bacterial Co-Existence

Author: Olaya Rendueles, Jorge A.M. de Sousa, Eduardo P.C. Rocha, Génomique évolutive des Microbes / Microbial Evolutionary Genomics, Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), This work was funded by an ANR JCJC (Agence national de recherche) grant [ANR 18 CE12 0001 01 ENCAPSULATION] awarded to O.R. The laboratory is funded by a Laboratoire d’Excellence ‘Integrative Biology of Emerging Infectious Diseases’ (grant ANR-10-LABX-62-IBEID) and the FRM [EQU201903007835]., The sequencing work was made at the Biomics Platform, C2RT, Institut Pasteur, Paris, France, supported by France Génomique (ANR-10-INBS-09) and IBISA., ANR-18-CE12-0001,ENCAPSULATION,Le rôle évolutif des capsules dans l'adaptation bactérienne(2018), and ANR-10-LABX-0062,IBEID,Integrative Biology of Emerging Infectious Diseases(2010)
Subjects: Interspecies competition, History, Polymers and Plastics, [SDE.BE]Environmental Sciences/Biodiversity and Ecology, Business and International Management, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, Industrial and Manufacturing Engineering
Abstract: Many bacterial species carry multiple prophages. Despite their potential cost, these elements can provide multiple fitness advantages to the host, such as the elimination of direct competitors. However, the long-term efficiency of prophage induction to displace competitors has received little attention. We experimentally coevolved a polylysogenic Klebsiella pneumoniae strain (ST14) with a phage-sensitive strain (BJ1) in several environments resulting in different phage pressures. We then followed the adaptation process and the emergence of resistance. After 30 days, population yield remained stable, and although BJ1 was present in all conditions, its frequency was higher when phage pressure was stronger. Resistance to phages emerged quickly through mutations that prevent capsule biosynthesis. In contrast to our expectation, lysogenic conversion was rare and costly because new BJ1 lysogens exhibited exacerbated death rates and were easily outcompeted. Unexpectedly, the adaptation process changed at longer time scales, where BJ1 populations adapted by fine-tuning the production of capsule, reducing the ability of phage to absorb, while remaining capsulated. These resistant clones are pan-resistant to a large panel of phages. Most intriguingly, some clones exhibited transient non-genetic resistance to phages. Our experimental and modelling results highlight the diversity, dynamics and competition between phage-resistance mechanisms during coevolution and how these are driven by phage pressure.
Published: 2022
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49. Phage-host coevolution in natural populations

Author: Damien Piel, Maxime Bruto, Yannick Labreuche, François Blanquart, David Goudenège, Rubén Barcia-Cruz, Sabine Chenivesse, Sophie Le Panse, Adèle James, Javier Dubert, Bruno Petton, Erica Lieberman, K. Mathias Wegner, Fatima A. Hussain, Kathryn M. Kauffman, Martin F. Polz, David Bikard, Sylvain Gandon, Eduardo P. C. Rocha, Frédérique Le Roux, Unité de Physiologie Fonctionnelle des Organismes Marins, Institut Français de Recherche pour l'Exploitation de la Mer (IFREMER), Laboratoire de Biologie Intégrative des Modèles Marins (LBI2M), Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Station biologique de Roscoff (SBR), Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), Centre interdisciplinaire de recherche en biologie (CIRB), Labex MemoLife, École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Collège de France (CdF (institution))-Ecole Superieure de Physique et de Chimie Industrielles de la Ville de Paris (ESPCI Paris), Université Paris sciences et lettres (PSL)-École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Infection, Anti-microbiens, Modélisation, Evolution (IAME (UMR_S_1137 / U1137)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)-Université Sorbonne Paris Nord, Universidade de Santiago de Compostela [Spain] (USC ), Fédération de recherche de Roscoff (FR2424), Station biologique de Roscoff (SBR), Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Department of Civil and Environmental Engineering [Cambridge] (CEE), Massachusetts Institute of Technology (MIT), Eligo Bioscience, Alfred-Wegener-Institut, Helmholtz-Zentrum für Polar- und Meeresforschung (AWI), Universität Wien, Biologie de Synthèse - Synthetic biology, Université Paris Cité (UPCité)-Microbiologie Intégrative et Moléculaire (UMR6047), Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre d’Ecologie Fonctionnelle et Evolutive (CEFE), Université Paul-Valéry - Montpellier 3 (UPVM)-École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD [France-Sud])-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Institut Agro Montpellier, Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Université de Montpellier (UM), Génomique évolutive des Microbes / Microbial Evolutionary Genomics, Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), We thank M. A. Petit, M. Blokesch, M. Sullivan and A. Bernheim for valuable suggestions, M. Touchon and A. Bernheim for assistance with vibrio genome annotation, Z. Chaplain for the illustrations and help during the time series sampling, the staff of the station Ifremer Argenton and Bouin, the ABIMS (Roscoff) and LABGeM (Evry) platforms for technical assistance, Z. Allouche, Biomics Platform, C2RT, Institut Pasteur, Paris, France, supported by France Génomique (ANR-10-INBS-09-09) and IBISA, and G. Riddihough from Life Science Editors for help with the manuscript. This work was supported by funding from the Agence Nationale de la Recherche (ANR-16-CE32-0008-01, REVENGE, ANR-20-CE35-0014, RESISTE), the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation programme (grant agreement No 884988, Advanced ERC Dynamic) to F.L.R. and Ifremer to D.P. The work was further supported by a grant from the Simons Foundation (LIFE ID 572792) to M.F.P. Part of the Vibrio crassostreae genome sequencing was conducted by the US Department of Energy Joint Genome Institute, a DOE Office of Science User Facility, and is supported by the Office of Science of the US Department of Energy under Contract No. DE-AC02-05CH11231. The funders had no role in study design, data collection and analysis, decision to publish or preparation of the manuscript., ANR-10-INBS-0009,France-Génomique,Organisation et montée en puissance d'une Infrastructure Nationale de Génomique(2010), ANR-16-CE32-0008,REVENGE,L'huître comme niche de l'évolution et l'émergence de vibrios pathogènes(2016), ANR-20-CE35-0014,RESISTE,Comprendre l'évolution de la résistance aux antimicrobiens chez les vibrios environnementaux(2020), European Project: 884988,ERC-2019-ADG,DYNAMIC(2021), Le Roux, Frédérique, Organisation et montée en puissance d'une Infrastructure Nationale de Génomique - - France-Génomique2010 - ANR-10-INBS-0009 - INBS - VALID, L'huître comme niche de l'évolution et l'émergence de vibrios pathogènes - - REVENGE2016 - ANR-16-CE32-0008 - AAPG2016 - VALID, Comprendre l'évolution de la résistance aux antimicrobiens chez les vibrios environnementaux - - RESISTE2020 - ANR-20-CE35-0014 - AAPG2020 - VALID, A mechanistic approach to understand microbiome-viriome dynamics in nature - DYNAMIC - - ERC-2019-ADG2021-01-01 - 2025-12-31 - 884988 - VALID, Université Paul-Valéry - Montpellier 3 (UPVM)-École Pratique des Hautes Études (EPHE), Physiologie Fonctionnelle des Organismes Marins (PFOM), Laboratoire de Biologie Intégrative (LBI), Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Laboratoire des Sciences de l'Environnement Marin (LEMAR) (LEMAR), Institut de Recherche pour le Développement (IRD)-Institut Français de Recherche pour l'Exploitation de la Mer (IFREMER)-Université de Brest (UBO)-Institut Universitaire Européen de la Mer (IUEM), Institut de Recherche pour le Développement (IRD)-Institut national des sciences de l'Univers (INSU - CNRS)-Université de Brest (UBO)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Institut national des sciences de l'Univers (INSU - CNRS)-Université de Brest (UBO)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), Alfred Wegener Institute for Polar and Marine Research (AWI), University of Vienna [Vienna], Institut Pasteur [Paris] (IP), and Génétique des génomes - Genetics of Genomes (UMR 3525)
Subjects: Water microbiology, Microbiology (medical), MESH: Host Specificity, [SDV.BID.EVO]Life Sciences [q-bio]/Biodiversity/Populations and Evolution [q-bio.PE], Immunology, Cell Biology, [SDV.EE.IEO] Life Sciences [q-bio]/Ecology, environment/Symbiosis, Applied Microbiology and Biotechnology, Microbiology, Host Specificity, [SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, Genetics, [SDV.BID.EVO] Life Sciences [q-bio]/Biodiversity/Populations and Evolution [q-bio.PE], Bacteriophages, MESH: Bacteriophages, [SDV.MP] Life Sciences [q-bio]/Microbiology and Parasitology, Viral genetics, Coevolution, [SDV.EE.IEO]Life Sciences [q-bio]/Ecology, environment/Symbiosis
Abstract: International audience; Coevolution between bacteriophages (phages) and their bacterial hosts occurs through changes in resistance and counter-resistance mechanisms. To assess phage-host evolution in wild populations, we isolated 195 Vibrio crassostreae strains and 243 vibriophages during a 5-month time series from an oyster farm and combined these isolates with existing V. crassostreae and phage isolates. Cross-infection studies of 81,926 host-phage pairs delineated a modular network where phages are best at infecting cooccurring hosts, indicating local adaptation. Successful propagation of phage is restricted by the ability to adsorb to closely related bacteria and further constrained by strain-specific defence systems. These defences are highly diverse and predominantly located on mobile genetic elements, and multiple defences are active within a single genome. We further show that epigenetic and genomic modifications enable phage to adapt to bacterial defences and alter host range. Our findings reveal that the evolution of Please note that this is an author-produced PDF of an article accepted for publication following peer review. The definitive publisher-authenticated version is available on the publisher Web site. bacterial defences and phage counter-defences is underpinned by frequent genetic exchanges with, and between, mobile genetic elements.
Published: 2022
Full Text: View/download PDF

50. PERFORM PROTOCOL TESTS AND SEQUENCE CHECKS ? THE EXPERIENCE FROM MULTIOMICS MICROBIOTA DATA

Author: Bernard, Maria, Coville, Jean-Luc, Bruneau, Nicolas, Jardet, Deborah, Calenge, Fanny, Pascal, Géraldine, Zerjal, Tatiana, BERNARD, Maria, Adaptation : des gènes aux populations. Génétique et biologie de l'adaptation aux stress et aux perturbations - Mécanismes d'adaptation à la chaleur et à un aliment suboptimal chez la poule pondeuse - - ChickStress2013 - ANR-13-ADAP-0014 - BIOADAPT - VALID, Adapting the feed, the animal and the feeding techniques to improve the efficiency and sustainability of monogastric livestock production systems - Feed-a-Gene - - H20202015-03-01 - 2020-02-29 - 633531 - VALID, Génétique Animale et Biologie Intégrative (GABI), AgroParisTech-Université Paris-Saclay-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Génétique Physiologie et Systèmes d'Elevage (GenPhySE ), Ecole Nationale Vétérinaire de Toulouse (ENVT), Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT)-Université de Toulouse (UT)-École nationale supérieure agronomique de Toulouse (ENSAT), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), France Génomique project MetaChick for metagenomic sequencing, INRAE AG department project ChickMetaT for metatranscriptomic, ANR-13-ADAP-0014,ChickStress,Mécanismes d'adaptation à la chaleur et à un aliment suboptimal chez la poule pondeuse(2013), and European Project: 633531,H2020,H2020-SFS-2014-2,Feed-a-Gene(2015)
Subjects: [SDE.BE] Environmental Sciences/Biodiversity and Ecology, [SDV.BID]Life Sciences [q-bio]/Biodiversity, [SDE.BE]Environmental Sciences/Biodiversity and Ecology, [SDV.BID] Life Sciences [q-bio]/Biodiversity
Abstract: International audience
Published: 2022

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