Descriptor: "MESH: Bacteria" - Searchworks@Jio Institute Digital Library Search Results

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303 results on '"MESH: Bacteria"'

1. Reclassification of family A DNA polymerases reveals novel functional subfamilies and distinctive structural features

Author: Dariusz Czernecki, Antonin Nourisson, Pierre Legrand, Marc Delarue, Architecture et Dynamique des Macromolécules Biologiques - Architecture and Dynamics of Biological Macromolecules, Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Ecole Doctorale Complexité du Vivant (ED515), Sorbonne Université (SU), Synchrotron SOLEIL (SSOLEIL), Centre National de la Recherche Scientifique (CNRS), We thank ANR (Grant ANR 20 CE11 002603 BreakDance) for travelling funds allowing the completion of this project., and ANR-20-CE11-0026,BreakDance,Caractérisation de la chorégraphie orchestrée par l'hétérodimère Ku sur les cassures double-brin de l'ADN(2020)
Subjects: MESH: Bacteria, MESH: Eukaryota, MESH: Archaea, [SDV]Life Sciences [q-bio], MESH: DNA-Directed DNA Polymerase, Genetics, MESH: Phylogeny, MESH: Uracil-DNA Glycosidase
Abstract: Family A DNA polymerases (PolAs) form an important and well-studied class of extant polymerases participating in DNA replication and repair. Nonetheless, despite the characterization of multiple subfamilies in independent, dedicated works, their comprehensive classification thus far is missing. We therefore re-examine all presently available PolA sequences, converting their pairwise similarities into positions in Euclidean space, separating them into 19 major clusters. While 11 of them correspond to known subfamilies, eight had not been characterized before. For every group, we compile their general characteristics, examine their phylogenetic relationships and perform conservation analysis in the essential sequence motifs. While most subfamilies are linked to a particular domain of life (including phages), one subfamily appears in Bacteria, Archaea and Eukaryota. We also show that two new bacterial subfamilies contain functional enzymes. We use AlphaFold2 to generate high-confidence prediction models for all clusters lacking an experimentally determined structure. We identify new, conserved features involving structural alterations, ordered insertions and an apparent structural incorporation of a uracil-DNA glycosylase (UDG) domain. Finally, genetic and structural analyses of a subset of T7-like phages indicate a splitting of the 3′–5′ exo and pol domains into two separate genes, observed in PolAs for the first time.
Published: 2023

2. Architecture and genomic arrangement of the MurE–MurF bacterial cell wall biosynthesis complex

Author: Karina T. Shirakawa, Fernanda Angélica Sala, Mayara M. Miyachiro, Viviana Job, Daniel Maragno Trindade, Andréa Dessen, Brazilian National Laboratory for Biosciences (LNBio), Centro Nacional de Pesquisa em Energia e materiais, Centra Nacional de Pesquisa-Centra Nacional de Pesquisa, Institut de biologie structurale (IBS - UMR 5075), Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), 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)-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), and Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Grenoble Alpes (UGA)
Subjects: Bordetella spp, MESH: Bacteria, MESH: Cell Wall, Multidisciplinary, chimeric proteins, MESH: Ligases, MESH: Peptidoglycan, MESH: Genomics, [SDV]Life Sciences [q-bio], peptidoglycan, MESH: Peptide Synthases, Mur ligases, MESH: Bacterial Proteins
Abstract: Peptidoglycan (PG) is a central component of the bacterial cell wall, and the disruption of its biosynthetic pathway has been a successful antibacterial strategy for decades. PG biosynthesis is initiated in the cytoplasm through sequential reactions catalyzed by Mur enzymes that have been suggested to associate into a multimembered complex. This idea is supported by the observation that in many eubacteria, mur genes are present in a single operon within the well conserved dcw cluster, and in some cases, pairs of mur genes are fused to encode a single, chimeric polypeptide. We performed a vast genomic analysis using >140 bacterial genomes and mapped Mur chimeras in numerous phyla, with Proteobacteria carrying the highest number. MurE–MurF, the most prevalent chimera, exists in forms that are either directly associated or separated by a linker. The crystal structure of the MurE–MurF chimera from Bordetella pertussis reveals a head-to-tail, elongated architecture supported by an interconnecting hydrophobic patch that stabilizes the positions of the two proteins. Fluorescence polarization assays reveal that MurE–MurF interacts with other Mur ligases via its central domains with K D s in the high nanomolar range, backing the existence of a Mur complex in the cytoplasm. These data support the idea of stronger evolutionary constraints on gene order when encoded proteins are intended for association, establish a link between Mur ligase interaction, complex assembly and genome evolution, and shed light on regulatory mechanisms of protein expression and stability in pathways of critical importance for bacterial survival.
Published: 2023

3. 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

4. An ancient divide in outer membrane tethering systems in bacteria suggests a mechanism for the diderm-to-monoderm transition

Author: Jerzy Witwinowski, Anna Sartori-Rupp, Najwa Taib, Nika Pende, To Nam Tham, Daniel Poppleton, Jean-Marc Ghigo, Christophe Beloin, Simonetta Gribaldo, Biologie Évolutive de la Cellule Microbienne - Evolutionary Biology of the Microbial Cell, 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), Plateforme BioImagerie Ultrastructurale – Ultrastructural BioImaging Platform (UTechS UBI), Institut Pasteur [Paris] (IP), Hub Bioinformatique et Biostatistique - Bioinformatics and Biostatistics HUB, Institut Pasteur [Paris] (IP)-Université Paris Cité (UPCité), Génétique des Biofilms - Genetics of Biofilms, This work was supported by funding from the French National Research Agency (ANR) (no. Fir-OM ANR-16-CE12-0010), the Institut Pasteur’s Programmes Transversaux de Recherche (no. PTR 39-16), the French government’s Investissement d’Avenir Program, Laboratoire d’Excellence’s Integrative Biology of Emerging Infectious Diseases (grant no. ANR-10-LABX-62-IBEID) and the Fondation pour la Recherche Médicale (grant no. DEQ20180339185). N.P. is funded by a Pasteur-Roux Postdoctoral Fellowship from the Institut Pasteur. We thank A. Jiménez-Fernández for help with Veillonella genetics techniques. We thank the UTechS Photonic BioImaging (Imagopole), C2RT, Institut Pasteur (Paris, France) and the France BioImaging infrastructure network supported by the ANR (no. ANR-10–INSB–04, Investments for the Future), and the Région Ile-de-France (program Domaine d’Intérêt Majeur-Malinf) for the use of the Zeiss LSM 780 Elyra PS1 microscope. We thank S. Tachon from the NanoImaging Core facility of the Center for Technological Resources and Research of Institut Pasteur for assistance with the tomography acquisitions at the Titan Krios microscope. We thank the French Government Programme Investissements d’Avenir France BioImaging (FBI, no. ANR-10-INSB-04-01) for equipment support. We thank M. Nilges and the Equipex CACSICE (Centre d’analyse de systèmes complexes dans les environnements complexes) for providing the Falcon II direct detector. We thank the IT department at Institut Pasteur, Paris, for providing computational and storage services (TARS cluster)., ANR-16-CE12-0010,Fir-OM,Firmicutes avec une membrane externe: vers des nouveaux modeles d'étude de la transition monodermes/didermes(2016), ANR-10-LABX-0062,IBEID,Integrative Biology of Emerging Infectious Diseases(2010), and ANR-10-INBS-0004,France-BioImaging,Développment d'une infrastructure française distribuée coordonnée(2010)
Subjects: Microbiology (medical), Bacteria, MESH: Peptidoglycan, Lipoproteins, Immunology, MESH: Periplasm, Peptidoglycan, Cell Biology, MESH: Lipoproteins, [SDV.BID.SPT]Life Sciences [q-bio]/Biodiversity/Systematics, Phylogenetics and taxonomy, Gram-Positive Bacteria, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, Applied Microbiology and Biotechnology, Microbiology, MESH: Gram-Positive Bacteria, MESH: Bacteria, Periplasm, Genetics, MESH: Phylogeny, Phylogeny
Abstract: International audience; Recent data support the hypothesis that Gram-positive bacteria (monoderms) arose from Gram-negative ones (diderms) through loss of the outer membrane (OM), but how this happened remains unknown. As tethering of the OM is essential for cell envelope stability in diderm bacteria, its destabilization may have been involved in this transition. In the present study, we present an in-depth analysis of the four known main OM-tethering systems across the Tree of Bacteria (ToB). We show that the presence of such systems follows the ToB with a bimodal distribution matching the deepest phylogenetic divergence between Terrabacteria and Gracilicutes. Whereas the lipoprotein peptidoglycan-associated lipoprotein (Pal) is restricted to the Gracilicutes, along with a more sporadic occurrence of OmpA, and Braun's lipoprotein is present only in a subclade of Gammaproteobacteria, diderm Terrabacteria display, as the main system, the OmpM protein. We propose an evolutionary scenario whereby OmpM represents a simple, ancestral OM-tethering system that was later replaced by one based on Pal after the emergence of the Lol machinery to deliver lipoproteins to the OM, with OmpA as a possible transition state. We speculate that the existence of only one main OM-tethering system in the Terrabacteria would have allowed the multiple OM losses specifically inferred in this clade through OmpM perturbation, and we provide experimental support for this hypothesis by inactivating all four ompM gene copies in the genetically tractable diderm Firmicute Veillonella parvula. High-resolution imaging and tomogram reconstructions reveal a non-lethal phenotype in which vast portions of the OM detach from the cells, forming huge vesicles with an inflated periplasm shared by multiple dividing cells. Together, our results highlight an ancient shift of OM-tethering systems in bacterial evolution and suggest a mechanism for OM loss and the multiple emergences of the monoderm phenotype from diderm ancestors.
Published: 2022

5. Multicenter Evaluation of the FilmArray Blood Culture Identification 2 Panel for Pathogen Detection in Bloodstream Infections

Author: François Caméléna, Gauthier Péan de Ponfilly, Hélène Pailhoriès, Lucas Bonzon, Alexandre Alanio, Thibaut Poncin, Matthieu Lafaurie, François Dépret, Emmanuel Cambau, Sylvain Godreuil, Rachel Chenouard, Alban Le Monnier, Hervé Jacquier, Béatrice Berçot, 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, Hôpitaux Universitaire Saint-Louis, Lariboisière, Fernand-Widal, Groupe Hospitalier Paris Saint-Joseph (hpsj), 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), SFR UA 4208 Interactions Cellulaires et Applications Thérapeutiques (ICAT), Université d'Angers (UA), Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM), Institut de Biologie en Santé (PHB-IRIS) [CHU Angers] (IBS), PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM), Maladies infectieuses et vecteurs : écologie, génétique, évolution et contrôle (MIVEGEC), Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD [France-Sud])-Université de Montpellier (UM), CHU Montpellier, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Mycologie Moléculaire, Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Hôpital Lariboisière-Fernand-Widal [APHP], Université Paris-Saclay, Centre hospitalier Saint-Joseph [Paris], Laboratoire de Parasitologie-Mycologie [CHU Saint Louis, Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Mycologie moléculaire - Molecular Mycology, Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Service de maladies infectieuses et tropicales [Saint-Louis], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Cité (UPCité), Hôpitaux Universitaires Saint-Louis, Lariboisière, Fernand-Widal, This study was supported by bioMérieux (Marcy L’Etoile, France), which providedconsumables. The funders had no role in study design, data collection and interpretation, ormanuscript preparation.F.C. received lecture fees from bioMérieux. F.D. received lecture fees from bioMérieuxand Sedana and grants from European Society of Intensive Care Medicine, Société Françaised’Anesthésie Reanimation, and the French Ministry of Research. A.A. received lecture feesand travel grants from Gilead Sciences and Pfizer and received grants from AgenceNationale de la Recherche. All other authors report no conflicts of interest., and bioMérieux (Marcy L’Etoile, France)European Society of Intensive Care MedicineSociété Française d’Anesthésie ReanimationFrench Ministry of Research. Gilead SciencesPfizerAgence Nationale de la Recherche
Subjects: Microbiology (medical), BCID2, [SDV.BIO]Life Sciences [q-bio]/Biotechnology, FilmArray, Physiology, [SDV]Life Sciences [q-bio], bloodstream infection, MESH: Blood Culture, BSI, MESH: Gram-Positive Bacteria, sepsis, Biofire, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, resistance gene, MESH: Gram-Negative Bacteria, molecular diagnosis, Genetics, MESH: Bacteremia, MESH: Sepsis, rapid diagnosis, genotypic identification, MESH: Humans, General Immunology and Microbiology, Ecology, Cell Biology, MESH: Bacteria, Infectious Diseases, [SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology
Abstract: International audience; The FilmArray Blood Culture Identification 2 panel (BCID2; bioMérieux) is a fully automated PCR-based assay for identifying bacteria, fungi, and bacterial resistance markers in positive blood cultures (BC) in about 1 h. In this multicenter study, we evaluated the performance of the BCID2 panel for pathogen detection in positive BC. Conventional culture and BCID2 were performed in parallel at four tertiary-care hospitals. We included 152 positive BC-130 monomicrobial and 22 polymicrobial cultures-in this analysis. The BCID2 assay correctly identified 90% (88/98) of Gram-negative and 89% (70/79) of Gram-positive bacteria. Five bacterial isolates targeted by the BCID2 panel and recovered from five positive BC, including three polymicrobial cultures, were missed by the BCID2 assay. Fifteen isolates were off-panel organisms, accounting for 8% (15/182) of the isolates obtained from BC. The mean positive percent agreement between the BCID2 assay and standard culture was 97% (95% confidence interval, 95 to 99%), with agreement ranging from 67% for Candida albicans to 100% for 17 targets included in the BCID2 panel. BCID2 also identified the blaCTX-M gene in seven BC, including one for which no extended-spectrum β-lactamase (ESBL)-producing isolate was obtained in culture. However, it failed to detect ESBL-encoding genes in three BC. Two of the 18 mecA/C genes detected by the BCID2 were not confirmed. No carbapenemase, mecA/C, or MREJ targets were detected. The median turnaround time was significantly shorter for BCID2 than for culture. The BCID2 panel may facilitate faster pathogen identification in bloodstream infections. IMPORTANCE Rapid molecular diagnosis combining the identification of pathogens and the detection of antibiotic resistance genes from positive blood cultures (BC) can improve the outcome for patients with bloodstream infections. The FilmArray BCID2 panel, an updated version of the original BCID, can detect 11 Gram-positive bacteria, 15 Gram-negative bacteria, 7 fungal pathogens, and 10 antimicrobial resistance genes directly from a positive BC. Here, we evaluated the real-life microbiological performance of the BCID2 assay in comparison to the results of standard methods used in routine practice at four tertiary care hospitals.
Published: 2023

6. Gut microbiome of the largest living rodent harbors unprecedented enzymatic systems to degrade plant polysaccharides

Author: Lucelia Cabral, Gabriela F. Persinoti, Douglas A. A. Paixão, Marcele P. Martins, Mariana A. B. Morais, Mariana Chinaglia, Mariane N. Domingues, Mauricio L. Sforca, Renan A. S. Pirolla, Wesley C. Generoso, Clelton A. Santos, Lucas F. Maciel, Nicolas Terrapon, Vincent Lombard, Bernard Henrissat, Mario T. Murakami, Architecture et fonction des macromolécules biologiques (AFMB), and Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)
Subjects: Dietary Fiber, DIETARY FIBER, MESH: Carbohydrate Metabolism, [SDV]Life Sciences [q-bio], DIVERSITY, MESH: Plants, General Physics and Astronomy, MESH: Rodentia, Crystallography, X-Ray, Lignin, MESH: Animals, MESH: Phylogeny, Phylogeny, Multidisciplinary, MESH: Symbiosis, Plants, Multidisciplinary Sciences, Science & Technology - Other Topics, GASTROINTESTINAL-TRACT, Carbohydrate Metabolism, Xylans, Glycoside Hydrolases, Science, GENOMES, Rodentia, General Biochemistry, Genetics and Molecular Biology, MESH: Gastrointestinal Microbiome, Polysaccharides, MESH: Glycoside Hydrolases, STRUCTURE REFINEMENT, Animals, BIOSYNTHESIS, CELL, Symbiosis, Science & Technology, SEQUENCES, Bacteria, Bacteroidetes, General Chemistry, MESH: Crystallography, X-Ray, MESH: Lignin, MESH: Bacteroidetes, Gastrointestinal Microbiome, MESH: Bacteria, MESH: Xylans, MESH: Polysaccharides, BETA-GLUCANS, MESH: Dietary Fiber, XYLANASE-Z
Abstract: The largest living rodent, capybara, can efficiently depolymerize and utilize lignocellulosic biomass through microbial symbiotic mechanisms yet elusive. Herein, we elucidate the microbial community composition, enzymatic systems and metabolic pathways involved in the conversion of dietary fibers into short-chain fatty acids, a main energy source for the host. In this microbiota, the unconventional enzymatic machinery from Fibrobacteres seems to drive cellulose degradation, whereas a diverse set of carbohydrate-active enzymes from Bacteroidetes, organized in polysaccharide utilization loci, are accounted to tackle complex hemicelluloses typically found in gramineous and aquatic plants. Exploring the genetic potential of this community, we discover a glycoside hydrolase family of β-galactosidases (named as GH173), and a carbohydrate-binding module family (named as CBM89) involved in xylan binding that establishes an unprecedented three-dimensional fold among associated modules to carbohydrate-active enzymes. Together, these results demonstrate how the capybara gut microbiota orchestrates the depolymerization and utilization of plant fibers, representing an untapped reservoir of enzymatic mechanisms to overcome the lignocellulose recalcitrance, a central challenge toward a sustainable and bio-based economy. ispartof: NATURE COMMUNICATIONS vol:13 issue:1 ispartof: location:England status: published
Published: 2022

7. 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

8. Larval habitat determines the bacterial and fungal microbiota of the mosquito vector Aedes aegypti

Author: Karima Zouache, Edwige Martin, Nil Rahola, Marc F Gangue, Guillaume Minard, Audrey Dubost, Van Tran Van, Laura Dickson, Diego Ayala, Louis Lambrechts, Claire Valiente Moro, Laboratoire d'Ecologie Microbienne - UMR 5557 (LEM), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Ecole Nationale Vétérinaire de Lyon (ENVL)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Centre International de Recherches Médicales de Franceville (CIRMF), Maladies infectieuses et vecteurs : écologie, génétique, évolution et contrôle (MIVEGEC), Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD [France-Sud])-Université de Montpellier (UM), Interactions Virus-Insectes - Insect-Virus Interactions (IVI), Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), University of Texas Medical Branch at Galveston, This work was primarily funded by the Agence Nationale de la Recherche (grant ANR-16-CE35-0004-01 to LL and CVM). It was also supported by the French Government's Investissement d'Avenir program Laboratoire d'Excellence Integrative Biology of Emerging Infectious Diseases (grant ANR-10-LABX-62-IBEID to LL)., ANR-16-CE35-0004,MOSQUIBIOTA,Contribution de la diversité bactérienne intestinale à la capacité vectorielle d'Aedes aegypti(2016), and ANR-10-LABX-0062,IBEID,Integrative Biology of Emerging Infectious Diseases(2010)
Subjects: animal structures, mosquito, Mosquito Vectors, Applied Microbiology and Biotechnology, Microbiology, larva, Aedes, parasitic diseases, microbiota, Animals, MESH: Microbiota, MESH: Animals, bacteria, Ecology, breeding site, fungi, MESH: Aedes, Plant Breeding, MESH: Bacteria, MESH: Plant Breeding, [SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology, MESH: Mosquito Vectors, mycobiota, MESH: Larva, Mycobiome, MESH: Mycobiome
Abstract: Mosquito larvae are naturally exposed to microbial communities present in a variety of larval development sites. Several earlier studies have highlighted that the larval habitat influences the composition of the larval bacterial microbiota. However, little information is available on their fungal microbiota, i.e. the mycobiota. In this study, we provide the first simultaneous characterization of the bacterial and fungal microbiota in field-collected Aedes aegypti larvae and their respective aquatic habitats. We evaluated whether the microbial communities associated with the breeding site may affect the composition of both the bacterial and fungal communities in Ae. aegypti larvae. Our results show a higher similarity in microbial community structure for both bacteria and fungi between larvae and the water in which larvae develop than between larvae from different breeding sites. This supports the hypothesis that larval habitat is a major factor driving microbial composition in mosquito larvae. Since the microbiota plays an important role in mosquito biology, unravelling the network of interactions that operate between bacteria and fungi is essential to better understand the functioning of the mosquito holobiont.
Published: 2022

9. Identification of a two-component regulatory system involved in antimicrobial peptide resistance in Streptococcus pneumoniae

Author: Aissatou Maty Diagne, Anaïs Pelletier, Claire Durmort, Agathe Faure, Kerstin Kanonenberg, Céline Freton, Adeline Page, Frédéric Delolme, Jaroslav Vorac, Sylvain Vallet, Laure Bellard, Corinne Vivès, Franck Fieschi, Thierry Vernet, Patricia Rousselle, Sébastien Guiral, Christophe Grangeasse, Jean-Michel Jault, Cédric Orelle, Microbiologie moléculaire et biochimie structurale / Molecular Microbiology and Structural Biochemistry (MMSB), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), Institut de biologie structurale (IBS - UMR 5075), Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), 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)-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 Grenoble Alpes (UGA), SFR Biosciences, École normale supérieure de Lyon (ENS de 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), Laboratoire de Biologie Tissulaire et d'ingénierie Thérapeutique UMR 5305 (LBTI), FINOVI foundation, AVIESAN, ANR-17-CE11-0045,SpABC-TCS,Mécanisme de résistance aux peptides antimicrobiens par un transporteur ABC couplé à un système de régulation à deux composants chez Streptococcus pneumoniae(2017), ANR-19-CE15-0011,LookingForPegase,A la recherche de protéines régulant des enzymes responsables de la synthèse du peptidoglycane(2019), École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Thomas, Frank, Mécanisme de résistance aux peptides antimicrobiens par un transporteur ABC couplé à un système de régulation à deux composants chez Streptococcus pneumoniae - - SpABC-TCS2017 - ANR-17-CE11-0045 - AAPG2017 - VALID, and A la recherche de protéines régulant des enzymes responsables de la synthèse du peptidoglycane - - LookingForPegase2019 - ANR-19-CE15-0011 - AAPG2019 - VALID
Subjects: Immunology, Microbiology, MESH: Membrane Transport Proteins, Bacterial Proteins, Virology, Drug Resistance, Bacterial, Genetics, Escherichia coli, [SDV.BBM] Life Sciences [q-bio]/Biochemistry, Molecular Biology, Humans, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, Molecular Biology, MESH: Bacterial Proteins, MESH: Gene Expression Regulation, Bacterial, MESH: Humans, Bacteria, MESH: Escherichia coli, MESH: Peptides, Membrane Transport Proteins, Gene Expression Regulation, Bacterial, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, MESH: Bacteria, Streptococcus pneumoniae, Parasitology, [SDV.MP.BAC] Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, Peptides, Antimicrobial Peptides, MESH: Antimicrobial Peptides, MESH: Streptococcus pneumoniae
Abstract: Two-component regulatory systems (TCS) are among the most widespread mechanisms that bacteria use to sense and respond to environmental changes. In the human pathogen Streptococcus pneumoniae, a total of 13 TCS have been identified and many of them have been linked to pathogenicity. Notably, TCS01 strongly contributes to pneumococcal virulence in several infection models. However, it remains one of the least studied TCS in pneumococci and its functional role is still unclear. In this study, we demonstrate that TCS01 cooperates with a BceAB-type ABC transporter to sense and induce resistance to structurally-unrelated antimicrobial peptides of bacterial origin that all target undecaprenyl-pyrophosphate or lipid II, which are essential precursors of cell wall biosynthesis. Even though tcs01 and bceAB genes do not locate in the same gene cluster, disruption of either of them equally sensitized the bacterium to the same set of antimicrobial peptides. We show that the key function of TCS01 is to upregulate the expression of the transporter, while the latter appears the main actor in resistance. Electrophoretic mobility shift assays further demonstrated that the response regulator of TCS01 binds to the promoter region of the bceAB genes, implying a direct control of these genes. The BceAB transporter was overexpressed and purified from E. coli. After reconstitution in liposomes, it displayed substantial ATPase and GTPase activities that were stimulated by antimicrobial peptides to which it confers resistance to, revealing new functional features of a BceAB-type transporter. Altogether, this inducible defense mechanism likely contributes to the survival of the opportunistic microorganism in the human host, in which competition among commensal microorganisms is a key determinant for effective host colonization and invasive path.
Published: 2022

10. High prevalence of small intestine bacteria overgrowth and asymptomatic carriage of enteric pathogens in stunted children in Antananarivo, Madagascar

Author: Collard, Jean-Marc, Andrianonimiadana, Lova, Habib, Azimdine, Rakotondrainipiana, Maheninasy, Andriantsalama, Prisca, Randriamparany, Ravaka, Rabenandrasana, M., Weill, François-Xavier, Sauvonnet, Nathalie, Randremanana, Rindra Vatosoa, Guillemot, Vincent, Vonaesch, Pascale, Sansonetti, Philippe, Bidault, Floran, Unité de Bactériologie Expérimentale [Antananarivo, Madagascar] (IPM), Institut Pasteur de Madagascar, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP), Unité d’Épidémiologie et de Recherche clinique [Antananarivo, Madagascar], Bactéries pathogènes entériques (BPE), Institut Pasteur [Paris] (IP), Pathogénie microbienne moléculaire, Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM), Hub Bioinformatique et Biostatistique - Bioinformatics and Biostatistics, This project was funded by the Total and Petram Foundations and by Institut Pasteur. LA, PA and RR wages were supported by the Total Foundation and MR wage by the Petram Foundation. PV was supported by an Early Postdoctoral Fellowship (P2EZP3_152159), an Advanced Postdoctoral Fellowship (P300PA_177876) as well as a Return Grant (P3P3PA_17877) from the Swiss National Science Foundation, a Roux-Cantarini Fellowship (2016), a L'Oréal-UNESCO for Women in Science France Fellowship (2017) and an Excellence Scholarship from the University of Basel (Forschungsfonds, 2019)., We wish to thank all participating families, the AFRIBIOTA Consortium, the participating hospitals in Antananarivo, as well as the Institut Pasteur, the Institut Pasteur de Madagascar, and members of the scientific advisory board for their continuous support, Prof. Jean-Louis Demarquez for training sessions to teach the local health professionals the methods used for duodenal aspirations, Aurélie Etienne for precious help with the clinical procedures and first aspirations performed, the field workers Tseheno Harisoa and Rado Andrianantenaina, as well as all implicated community health workers, for countless hours spent in the field, and the Centre de Recherche Translationelle and the Direction Internationale of the Institut Pasteur, and especially Paméla Palvadeau, Jane Lynda Deuve, Marc Rovatiana Ranarijesy, Kanto Liantsoa Razanakolona, Cécile Artaud, Nathalie Jolly, Sophie Jarrijon, Mamy Ratsialonina, Jean-François Damaras, Marie-Noelle Ungeheuer, and Laurence Arowas for precious help in setting up and steering the AFRIBIOTA project and managing the funds and the biobank. We would like to thank the staff of the 'Plateforme de Microbiologie Mutualisée (P2M)' at Institut Pasteur Paris where the whole genome sequencing was performed, Sophie Lefevre from the Centre National de Référence des Escherichia coli, Shigella et Salmonella in Paris, France for Shigella serotyping, and Claude Parsot and Alexandre Grassart for the interesting discussions on Shigella.
Subjects: Adult, Diarrhea, MESH: Intestine, Small, MESH: Bacterial Infections, MESH: Shigella, MESH: Madagascar, Feces, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, MESH: Child, Intestine, Small, Escherichia coli, Madagascar, Prevalence, Humans, Child, MESH: Prevalence, MESH: Humans, Bacteria, MESH: Escherichia coli, digestive, oral, and skin physiology, Public Health, Environmental and Occupational Health, MESH: Feces, MESH: Adult, Bacterial Infections, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, MESH: Bacteria, MESH: Diarrhea, Infectious Diseases, [SDV.MHEP.MI] Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Shigella, [SDV.MP.BAC] Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology
Abstract: Environmental Enteric Dysfunction (EED) refers to an incompletely defined syndrome of inflammation, reduced absorptive capacity, and reduced barrier function in the small intestine. It is widespread among children and adults in low- and middle-income countries and is also associated with poor sanitation and certain gut infections possibly resulting in an abnormal gut microbiota, small intestinal bacterial overgrowth (SIBO) and stunting. We investigated bacterial pathogen exposure in stunted and non-stunted children in Antananarivo, Madagascar by collecting fecal samples from 464 children (96 severely stunted, 104 moderately stunted and 264 non-stunted) and the prevalence of SIBO in 109 duodenal aspirates from stunted children (61 from severely stunted and 48 from moderately stunted children). SIBO assessed by both aerobic and anaerobic plating techniques was very high: 85.3% when selecting a threshold of ≥105 CFU/ml of bacteria in the upper intestinal aspirates. Moreover, 58.7% of the children showed more than 106 bacteria/ml in these aspirates. The most prevalent cultivated genera recovered were Streptococcus, Neisseria, Staphylococcus, Rothia, Haemophilus, Pantoea and Branhamella. Feces screening by qPCR showed a high prevalence of bacterial enteropathogens, especially those categorized as being enteroinvasive or causing mucosal disruption, such as Shigella spp., enterotoxigenic Escherichia coli, enteropathogenic E. coli and enteroaggregative E. coli. These pathogens were detected at a similar rate in stunted children and controls, all showing no sign of severe diarrhea the day of inclusion but both living in a highly contaminated environment (slum-dwelling). Interestingly Shigella spp. was the most prevalent enteropathogen found in this study (83.3%) without overrepresentation in stunted children.
Published: 2022

11. Bacterial Approaches for Assembling Iron-Sulfur Proteins

Author: Frédéric Barras, Sarah Dubrac, Jeffrey M. Boyd, Karla Esquilin-Lebron, Rutgers, The State University of New Jersey [New Brunswick] (RU), Rutgers University System (Rutgers), Adaptation au stress et Métabolisme chez les entérobactéries - Stress adaptation and metabolism in enterobacteria (SAMe), 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), Université Paris Cité (UPCité), Support to the Barras lab was provided by the ANR-10-LABX-62-IBEID and the Pasteur Institute. The Boyd lab is funded by National Science Foundation award 1750624., and ANR-10-LABX-0062,IBEID,Integrative Biology of Emerging Infectious Diseases(2010)
Subjects: iron utilization, Iron-Sulfur Proteins, [SDV]Life Sciences [q-bio], metalloproteins, Iron, Iron–sulfur cluster, Computational biology, Microbiology, Genome, Defective assembly, genetic regulation, metalloregulation, iron-sulfur cluster, 03 medical and health sciences, chemistry.chemical_compound, Bacterial Proteins, ISC, iron regulation, Virology, Metalloprotein, MESH: Bacterial Proteins, Protein maturation, Gene, SUF, 030304 developmental biology, chemistry.chemical_classification, MESH: Iron, 0303 health sciences, sulfide, Bacteria, biology, 030306 microbiology, NIF, MESH: Iron-Sulfur Proteins, QR1-502, MESH: Sulfur, MESH: Bacteria, Iron-sulfur protein, chemistry, sulfur, biology.protein, Minireview
Abstract: International audience; Building iron-sulfur (Fe-S) clusters and assembling Fe-S proteins are essential actions for life on Earth. The three processes that sustain life, photosynthesis, nitrogen fixation, and respiration, require Fe-S proteins. Genes coding for Fe-S proteins can be found in nearly every sequenced genome. Fe-S proteins have a wide variety of functions, and therefore, defective assembly of Fe-S proteins results in cell death or global metabolic defects. Compared to alternative essential cellular processes, there is less known about Fe-S cluster synthesis and Fe-S protein maturation. Moreover, new factors involved in Fe-S protein assembly continue to be discovered. These facts highlight the growing need to develop a deeper biological understanding of Fe-S cluster synthesis, holo-protein maturation, and Fe-S cluster repair. Here, we outline bacterial strategies used to assemble Fe-S proteins and the genetic regulation of these processes. We focus on recent and relevant findings and discuss future directions, including the proposal of using Fe-S protein assembly as an antipathogen target.
Published: 2021

12. Intestinal Bacteriophage Therapy: Looking for Optimal Efficacy

Author: Chloé Latour, Quentin Lamy-Besnier, François Javaudin, Laurent Debarbieux, Microbiotes, Hôtes, Antibiotiques et Résistances bactériennes (MiHAR) (MiHAR), Nantes Université - UFR de Médecine et des Techniques Médicales (Nantes Univ - UFR MEDECINE), Nantes Université - pôle Santé, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ)-Nantes Université - pôle Santé, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ), Service des Urgences [CHU Nantes], Hôtel-Dieu de Nantes, Centre Hospitalier Centre Bretagne [Pontivy] (CHCB Pontivy), 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), This research was supported by funding to L.D. from ANR-20-CE92-0048. Q.L.-B. is funded by École Doctorale FIRE-Program Bettencourt., We thank Pierre Chauvet for help with the illustrations and Patrick Lane (ScEYEnce Studios) for graphical enhancement., and 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)
Subjects: Microbiology (medical), Epidemiology, medicine.drug_class, Antibiotics, Disease, Review, enteric pathogens, MESH: Phage Therapy, MESH: Gastrointestinal Microbiome, Microbiology, Bacteriophage, Animal model, MESH: Anti-Bacterial Agents, medicine, Animals, Humans, Bacteriophages, MESH: Animals, Phage Therapy, MESH: Bacteriophages, MESH: Humans, General Immunology and Microbiology, biology, Bacteria, Public Health, Environmental and Occupational Health, intestinal colonization, biology.organism_classification, Treatment efficacy, Anti-Bacterial Agents, Gastrointestinal Microbiome, MESH: Bacteria, Infectious Diseases, Bacteriophage Therapy, [SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology, Intestinal bacteria, gastrointestinal infection
Abstract: International audience; Several human intestinal microbiota studies suggest that bacteriophages, viruses infecting bacteria, play a role in gut homeostasis. Currently, bacteriophages are considered a tool to precisely engineer the intestinal microbiota, but they have also attracted considerable attention as a possible solution to fight against bacterial pathogens resistant to antibiotics. These two applications necessitate bacteriophages to reach and kill their bacterial target within the gut environment. Unfortunately, exploitable clinical data in this field are scarce. Here, we review the administration of bacteriophages to target intestinal bacteria in mammalian experimental models. While bacteriophage amplification in the gut was often confirmed, we found that in most studies, it had no significant impact on the load of the targeted bacteria. In particular, we observed that the outcome of bacteriophage treatments is linked to the behavior of the target bacteria toward each animal model. Treatment efficacy ranges from poor in asymptomatic intestinal carriage to high in intestinal disease. This broad range of efficacy underlines the difficulties to reach a consensus on the impact of bacteriophages in the gut and calls for deeper investigations of key parameters that influence the success of such interventions before launching clinical trials.
Published: 2021

13. Strainberry: automated strain separation in low-complexity metagenomes using long reads

Author: Vicedomini, Riccardo, Quince, Christopher, Darling, Aaron E., Chikhi, Rayan, Algorithmes pour les séquences biologiques - Sequence Bioinformatics, Institut Pasteur [Paris] (IP)-Université Paris Cité (UPCité), Warwick Medical School, University of Warwick [Coventry], Earlham Institute [Norwich], Quadram Institute, Biotechnology and Biological Sciences Research Council (BBSRC), iThree Institute, University of Technology Sydney (UTS), R.V. and R.C. are funded by ANR INCEPTION (PIA/ANR-16-CONV-0005) and R.C. by ANR PRAIRIE (ANR-19-P3IA-0001) and ANR SeqDigger (ANR-19-CE45-0008). C.Q. is funded through 'Strain resolved metagenomics for medical microbiology' MRC MR/S037195/1 and the 'CLIMB-BIG-DATA' consortium MR/T030062/1. A.E.D.’s contributions to this research were supported in part by the Australian Government through the Australian Research Council Discovery Projects funding scheme (project DP180101506)., ANR-16-CONV-0005,INCEPTION,Institut Convergences pour l'étude de l'Emergence des Pathologies au Travers des Individus et des populatiONs(2016), ANR-19-P3IA-0001,PRAIRIE,PaRis Artificial Intelligence Research InstitutE(2019), ANR-19-CE45-0008,SeqDigger,Moteur de recherche de donne´es de se´quenc¸age en ge´nomique environnementale(2019), and Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS)
Subjects: Bacteria, Bioinformatics, Science, MESH: Genomics, Computational Biology, High-Throughput Nucleotide Sequencing, Genomics, MESH: Metagenome, MESH: Genome, Bacterial, Article, MESH: Bacteria, Species Specificity, Genome assembly algorithms, Metagenome, MESH: Species Specificity, Metagenomics, MESH: Metagenomics, [INFO.INFO-BI]Computer Science [cs]/Bioinformatics [q-bio.QM], MESH: High-Throughput Nucleotide Sequencing, Software, Genome, Bacterial, MESH: Computational Biology
Abstract: High-throughput short-read metagenomics has enabled large-scale species-level analysis and functional characterization of microbial communities. Microbiomes often contain multiple strains of the same species, and different strains have been shown to have important differences in their functional roles. Recent advances on long-read based methods enabled accurate assembly of bacterial genomes from complex microbiomes and an as-yet-unrealized opportunity to resolve strains. Here we present Strainberry, a metagenome assembly pipeline that performs strain separation in single-sample low-complexity metagenomes and that relies uniquely on long-read data. We benchmarked Strainberry on mock communities for which it produces strain-resolved assemblies with near-complete reference coverage and 99.9% base accuracy. We also applied Strainberry on real datasets for which it improved assemblies generating 20-118% additional genomic material than conventional metagenome assemblies on individual strain genomes. We show that Strainberry is also able to refine microbial diversity in a complex microbiome, with complete separation of strain genomes. We anticipate this work to be a starting point for further methodological improvements on strain-resolved metagenome assembly in environments of higher complexities., Existing long-read de novo assembly methods can partially, but not completely, separate strains. Here, the authors develop Strainberry, a metagenome assembly bioinformatic pipeline that exclusively uses longread data to accurately separate and reconstruct strain genomes from single-sample low-complexity microbiomes.
Published: 2021

14. Microbiome-pathogen interactions drive epidemiological dynamics of antibiotic resistance: A modeling study applied to nosocomial pathogen control

Author: Smith, DR, Temime, L, Opatowski, L, Epidémiologie et modélisation de la résistance aux antimicrobiens - Epidemiology and modelling of bacterial escape to antimicrobials (EMAE), Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre de recherche en épidémiologie et santé des populations (CESP), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, Laboratoire Modélisation, épidémiologie et surveillance des risques sanitaires (MESuRS), Conservatoire National des Arts et Métiers [CNAM] (CNAM), Pasteur-Cnam Risques infectieux et émergents (PACRI), Institut Pasteur [Paris]-Conservatoire National des Arts et Métiers [CNAM] (CNAM), Institut Pasteur [Paris] (IP)-Université Paris Cité (UPCité), HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM), Institut Pasteur [Paris] (IP)-Conservatoire National des Arts et Métiers [CNAM] (CNAM), HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-Université Paris Cité (UPCité), The work was supported directly by internal resources from the French National Institute for Health and Medical Research, the Institut Pasteur, the Conservatoire National des Arts et Métiers, and the University of Versailles–Saint-Quentin-en-Yvelines / University of Paris-Saclay. This study received funding from the French Government’s ‘Investissement d’Avenir’ program, Laboratoire d’Excellence ‘Integrative Biology of Emerging Infectious Diseases’ (Grant ANR-10-LABX-62- IBEID). DS is supported by a Canadian Institutes of Health Research Doctoral Foreign Study Award (Funding Reference Number 164263) and all authors are supported by the French government through its National Research Agency project SPHINX-17-CE36-0008-01., ANR-10-LABX-0062,IBEID,Integrative Biology of Emerging Infectious Diseases(2010), ANR-17-CE36-0008,SPHINx,Diffusion de pathogènes au sein des réseaux de soins : une étude de modélisation(2017), Bertram, Marie-Liesse, Integrative Biology of Emerging Infectious Diseases - - IBEID2010 - ANR-10-LABX-0062 - LABX - VALID, and Diffusion de pathogènes au sein des réseaux de soins : une étude de modélisation - - SPHINx2017 - ANR-17-CE36-0008 - AAPG2017 - VALID
Subjects: MESH: Drug Resistance, Microbial, QH301-705.5, Science, global health, antibiotics, K. pneumoniae, MESH: Anti-Bacterial Agents, microbiota, Humans, MESH: Microbiota, human, Biology (General), MESH: Models, Theoretical, Cross Infection, MESH: Humans, Bacteria, E. coli, MESH: Cross Infection, Drug Resistance, Microbial, Models, Theoretical, S. aureus, within-host interactions, Anti-Bacterial Agents, MESH: Bacteria, Epidemiology and Global Health, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, Medicine, epidemiology, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, Other, C. difficile, ecology, Research Article
Abstract: International audience; The human microbiome can protect against colonization with pathogenic antibiotic-resistant bacteria (ARB), but its impacts on the spread of antibiotic resistance are poorly understood. We propose a mathematical modeling framework for ARB epidemiology formalizing within-host ARB-microbiome competition, and impacts of antibiotic consumption on microbiome function. Applied to the healthcare setting, we demonstrate a trade-off whereby antibiotics simultaneously clear bacterial pathogens and increase host susceptibility to their colonization, and compare this framework with a traditional strain-based approach. At the population level, microbiome interactions drive ARB incidence, but not resistance rates, reflecting distinct epidemiological relevance of different forces of competition. Simulating a range of public health interventions (contact precautions, antibiotic stewardship, microbiome recovery therapy) and pathogens ( Clostridioides difficile , methicillin-resistant Staphylococcus aureus , multidrug-resistant Enterobacteriaceae) highlights how species-specific within-host ecological interactions drive intervention efficacy. We find limited impact of contact precautions for Enterobacteriaceae prevention, and a promising role for microbiome-targeted interventions to limit ARB spread.
Published: 2021

15. Pressure ulcers microbiota dynamics and wound evolution

Author: Maxime Brunaud, Anthony Gelis, Jean-Philippe Lavigne, Christophe Demattei, Alex Yahiaoui-Martinez, Florian Salipante, Catherine Dunyach-Remy, Sophie Bastide, Claire Palayer, Albert Sotto, Centre Hospitalier Universitaire de Nîmes (CHU Nîmes), Virulence bactérienne et maladies infectieuses (VBMI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Laboratoire de Biostatistique, Epidémiologie clinique, Santé Publique Innovation et Méthodologie [CHU Nîmes] (BESPIM), Hôpital Universitaire Carémeau [Nîmes] (CHU Nîmes), Centre Hospitalier Universitaire de Nîmes (CHU Nîmes)-Centre Hospitalier Universitaire de Nîmes (CHU Nîmes), Institut Desbrest de santé publique (IDESP), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Dynamique des capacités humaines et des conduites de santé (EPSYLON), Université Paul-Valéry - Montpellier 3 (UPVM), and Retiveau, Nolwenn
Subjects: Male, Finegoldia, Peptoniphilus, medicine.disease_cause, Gastroenterology, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, RNA, Ribosomal, 16S, Spinal cord injury, MESH: Aged, Pressure Ulcer, MESH: Middle Aged, Multidisciplinary, biology, Microbiota, Middle Aged, MESH: RNA, Ribosomal, 16S, Cohort, [SDV.MHEP.MI] Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Medicine, Female, Infection, medicine.medical_specialty, MESH: Pressure Ulcer, food.ingredient, Science, Microbial communities, Article, food, Morganella, Internal medicine, medicine, MESH: Microbiota, Humans, Clinical microbiology, Aged, Wound Healing, MESH: Humans, Bacteria, business.industry, Anaerococcus, [SDV.MHEP.DERM] Life Sciences [q-bio]/Human health and pathology/Dermatology, biology.organism_classification, medicine.disease, MESH: Male, MESH: Bacteria, MESH: Wound Healing, Proteus, Bacterial infection, business, MESH: Female, Staphylococcus, [SDV.MHEP.DERM]Life Sciences [q-bio]/Human health and pathology/Dermatology
Abstract: Bacterial species and their role in delaying the healing of pressure ulcers (PU) in spinal cord injury (SCI) patients have not been well described. This pilot study aimed to characterise the evolution of the cutaneous microbiota of PU in SCI cohort. Twenty-four patients with SCI from a French neurological rehabilitation centre were prospectively included. PU tissue biopsies were performed at baseline (D0) and 28 days (D28) and analysed using 16S rRNA gene-based sequencing analysis of the V3–V4 region. At D0, if the overall relative abundance of genus highlighted a large proportion of Staphylococcus, Anaerococcus and Finegoldia had a significantly higher relative abundance in wounds that stagnated or worsened in comparison with those improved at D28 (3.74% vs 0.05%; p = 0.015 and 11.02% versus 0.16%; p = 0.023, respectively). At D28, Proteus and Morganella genera were only present in stagnated or worsened wounds with respectively 0.02% (p = 0.003) and 0.01% (p = 0.02). Moreover, Proteus, Morganella, Anaerococcus and Peptoniphilus were associated within the same cluster, co-isolated from biopsies that had a poor evolution. This pathogroup could be a marker of wound degradation and Proteus could represent a promising target in PU management.
Published: 2021

16. Generating High-Resolution Hi-C Contact Maps of Bacteria

Author: Charlotte Cockram, Agnès Thierry, Régulation spatiale des Génomes - Spatial Regulation of Genomes, Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), This research was supported by funding to Romain Koszul from the Agence Nationale pour la Recherche (HiResBac ANR-15-CE11-0023-03) and from the European Research Council under the Horizon 2020 program (ERC grant agreement: 771813)., We thank Romain Koszul and the members of the RSG lab for insightful discussions regarding the development of this protocol., ANR-15-CE11-0023,HiResBaCS,Structure des chromosomes bactériens revélée a haute résolution(2015), and European Project: 771813,ERC-2017-COG,SynarchiC(2018)
Subjects: Chromosome conformation capture, biology, Bacteria, Computer science, [SDV]Life Sciences [q-bio], Resolution (electron density), High resolution, Computational biology, Bacterial genome size, biology.organism_classification, Genome organization, MESH: Gram-Positive Bacteria, MESH: Bacteria, MESH: Software, Chromosome (genetic algorithm), Hi-C, MESH: Anti-Bacterial Agents, MESH: Gram-Negative Bacteria, MESH: Chromosomes, Prokaryotes, 3C, Genomic organization
Abstract: International audience; During the past decade, Chromosome Conformation Capture (3C/Hi-C)-based methods have been used to probe the 3D structure and organization of bacterial genomes, revealing fundamental aspects of chromosome dynamics. However, the current protocols are expensive, inefficient, and limited in their resolution. Here we present a simple, cost-effective Hi-C approach that is readily applicable to a range of Gram-positive and Gram-negative bacteria.
Published: 2021

17. The evolution and role of eukaryotic-like domains in environmental intracellular bacteria: the battle with a eukaryotic cell

Author: Jessica E Martyn, Laura Gomez-Valero, Carmen Buchrieser, Biologie des Bactéries intracellulaires - Biology of Intracellular Bacteria, 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), Work in the CB laboratory is financed by the Institut Pasteur, the Fondation pour la Recherche Médicale (FRM) grant no. EQU201903007847 and the Agence Nationale de la Recherche grant no. ANR-10-LABX-62-IBEID. JEM was supported by a post-doctoral fellowship Fondation pour la Recherche Médicale (FRM)., We thank Christophe Rusniok for his help for the bioinformatics analyses shown in Fig. 1 and Table 1, and Suzanna Salcedo for her patience in waiting for this manuscript that was prepared during three consecutive Covid lockdowns., and ANR-10-LABX-0062,IBEID,Integrative Biology of Emerging Infectious Diseases(2010)
Subjects: Bacteria, intracellular bacteria, [SDV]Life Sciences [q-bio], MESH: Host-Pathogen Interactions, Eukaryota, Legionella, eukaryotic-like domains, MESH: Eukaryotic Cells, Microbiology, virulence, MESH: Bacteria, MESH: Eukaryota, [SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology, Infectious Diseases, Eukaryotic Cells, Bacterial Proteins, evolution, Host-Pathogen Interactions, horizontal gene transfer, Animals, MESH: Animals, Chlamydia, MESH: Bacterial Proteins, MESH: Legionella
Abstract: International audience; One sentence summary: This review aims to dissect the evolutionary processes that may lead to an enrichment of eukaryotic-like proteins in environmental intracellular bacteria through continuous adaptation to multiple eukaryotic hosts. We reveal that chromatin and ubiquitin modulation functions, as well as adaptable tandem repeat domains, are crucial for their virulence in protozoa and accidentally also in humans.Intracellular pathogens that are able to thrive in different environments, such as Legionella spp. that preferentially live in protozoa in aquatic environments or environmental Chlamydiae that replicate either within protozoa or a range of animals, possess a plethora of cellular biology tools to influence their eukaryotic host. The host manipulation tools that evolved in the interaction with protozoa confer these bacteria the capacity to also infect phylogenetically distinct eukaryotic cells, such as macrophages, and thus they can also be human pathogens. To manipulate the host cell, bacteria use protein secretion systems and molecular effectors. Although these molecular effectors are encoded in bacteria, they are expressed and function in a eukaryotic context often mimicking or inhibiting eukaryotic proteins. Indeed, many of these effectors have eukaryotic-like domains. In this review, we propose that the main pathways that environmental intracellular bacteria need to subvert in order to establish the host eukaryotic cell as a replication niche are chromatin remodelling, ubiquitination signalling and modulation of protein–protein interactions via tandem repeat domains. We then provide mechanistic insight into how these proteins might have evolved. Finally, we highlight that in environmental intracellular bacteria the number of eukaryotic-like domains and proteins is considerably higher than in intracellular bacteria specialized to an isolated niche, such as obligate intracellular human pathogens. As mimics of eukaryotic proteins are critical components of host–pathogen interactions, this distribution of eukaryotic-like domains suggests that the environment has selected them.
Published: 2021

18. CRISPRCasdb a successor of CRISPRdb containing CRISPR arrays and cas genes from complete genome sequences, and tools to download and query lists of repeats and spacers

Author: Jean-Philippe Vernadet, Christine Pourcel, David Couvin, Marie Touchon, Gilles Vergnaud, Nicolas Villeriot, Claire Toffano-Nioche, 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), Génomique évolutive des Microbes / Microbial Evolutionary Genomics, Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Unité Transmission, Réservoir et Diversité des Pathogènes [Pasteur Guadeloupe, France] (TReD-Path), Institut Pasteur de la Guadeloupe, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP), Institut Français de Bioinformatique (IFB) [ANR-11-INSB-0013]. Funding for open access charge: CNRS., Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Séquence, Structure et Fonction des ARN (SSFA), Département Biologie des Génomes (DBG), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)-Institut de Biologie Intégrative de la Cellule (I2BC), and Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)
Subjects: Transposable element, MESH: CRISPR-Cas Systems, MESH: Genome, Archaeal, [SDV]Life Sciences [q-bio], CRISPR-Associated Proteins, Computational biology, MESH: Genome, Bacterial, Genome, 03 medical and health sciences, MESH: Software, Plasmid, Phylogenetics, Genome, Archaeal, Databases, Genetic, Genetics, CRISPR, Database Issue, Clustered Regularly Interspaced Short Palindromic Repeats, MESH: Phylogeny, Gene, MESH: Databases, Genetic, Phylogeny, 030304 developmental biology, 0303 health sciences, biology, Bacteria, 030306 microbiology, MESH: CRISPR-Associated Proteins, Palindrome, Prokaryote, biology.organism_classification, [SDV.BIBS]Life Sciences [q-bio]/Quantitative Methods [q-bio.QM], Archaea, MESH: Bacteria, MESH: Archaea, MESH: Clustered Regularly Interspaced Short Palindromic Repeats, CRISPR-Cas Systems, Genome, Bacterial, Software
Abstract: In Archaea and Bacteria, the arrays called CRISPRs for ‘clustered regularly interspaced short palindromic repeats’ and the CRISPR associated genes or cas provide adaptive immunity against viruses, plasmids and transposable elements. Short sequences called spacers, corresponding to fragments of invading DNA, are stored in-between repeated sequences. The CRISPR–Cas systems target sequences homologous to spacers leading to their degradation. To facilitate investigations of CRISPRs, we developed 12 years ago a website holding the CRISPRdb. We now propose CRISPRCasdb, a completely new version giving access to both CRISPRs and cas genes. We used CRISPRCasFinder, a program that identifies CRISPR arrays and cas genes and determine the system's type and subtype, to process public whole genome assemblies. Strains are displayed either in an alphabetic list or in taxonomic order. The database is part of the CRISPR-Cas++ website which also offers the possibility to analyse submitted sequences and to download programs. A BLAST search against lists of repeats and spacers extracted from the database is proposed. To date, 16 990 complete prokaryote genomes (16 650 bacteria from 2973 species and 340 archaea from 300 species) are included. CRISPR–Cas systems were found in 36% of Bacteria and 75% of Archaea strains. CRISPRCasdb is freely accessible at https://crisprcas.i2bc.paris-saclay.fr/.
Published: 2019

19. Whole genome sequencing reveals resemblance between ESBL-producing and carbapenem resistant Klebsiella pneumoniae isolates from Austrian rivers and clinical isolates from hospitals

Author: Rainer Hartl, Heidrun Kerschner, Burkhard Springer, Sieglinde Sorschag, Franz Allerberger, Sarah Lepuschitz, Norbert Inreiter, Simone Schill, Steliana Huhulescu, Sylvain Brisse, Werner Ruppitsch, Robert L. Mach, Anna Stoeger, Shiva Pekard-Amenitsch, Austrian Agency for Health and Food Safety (AGES), Vienna University of Technology (TU Wien), Ordensklinikum Linz Elisabethinen, Klinikum Klagenfurt am Wörthersee, Biodiversité et Epidémiologie des Bactéries pathogènes - Biodiversity and Epidemiology of Bacterial Pathogens, Institut Pasteur [Paris] (IP), Universität für Bodenkultur Wien = University of Natural Resources and Life [Vienne, Autriche] (BOKU), This work was partially funded by a grant to S.L. by the Austrian Society for Antimicrobial Chemotherapy (ÖGACH). Part of the sequencing-work was supported financially by the MedVetKlebs project, a component of the One Health European Joint Programme, which has received funding from the European Union's Horizon 2020 research and innovation programme under Grant Agreement No 773830., We thank the team of curators of the Institut Pasteur MLST and whole genome MLST databases for curating the data and making them publicly available at http://bigsdb.pasteur.fr/., European Project: 773830,H2020-SFS-2017-1,MedVetKlebs (a component of European Joint Programme One Health)(2018), Institut Pasteur [Paris], University of Natural Resources and Life Sciences (BOKU), and European Project: 773830,H2020-SFS-2017-1,MedVetKlebs (a component of European Joint Programme One Health EJP)(2018)
Subjects: Veterinary medicine, 010504 meteorology & atmospheric sciences, MESH: beta-Lactamases, Pilot Projects, Drug resistance, 010501 environmental sciences, 01 natural sciences, Surface-water, MESH: Carbapenems, Drug Resistance, Multiple, Bacterial, MESH: Bacterial Proteins, Waste Management and Disposal, Antiinfective agent, Surveillance, Multiresistance Anthropogenic pollution Surface-water Surveillance Whole-genome sequencing, MESH: Hospitals, Pollution, Hospitals, 6. Clean water, Subtyping, Anti-Bacterial Agents, 3. Good health, MESH: Multilocus Sequence Typing, Austria, MESH: Whole Genome Sequencing, Environmental Engineering, Anthropogenic pollution, Locus (genetics), [SDV.BID]Life Sciences [q-bio]/Biodiversity, Biology, beta-Lactamases, MESH: Rivers, Antibiotic resistance, Bacterial Proteins, Rivers, MESH: Anti-Bacterial Agents, Environmental Chemistry, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, Typing, Multiresistance, 0105 earth and related environmental sciences, Whole genome sequencing, Whole-genome sequencing, Bacteria, Whole Genome Sequencing, MESH: Drug Resistance, Multiple, Bacterial, MESH: Pilot Projects, Multiple drug resistance, MESH: Bacteria, Carbapenems, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, MESH: Austria, Multilocus Sequence Typing
Abstract: International audience; In 2016, the Austrian Agency for Health and Food Safety started a pilot project to investigate antimicrobial resistance in surface water. Here we report on the characterisation of carbapenem resistant and ESBL-producing K. pneumoniae isolates from Austrian river water samples compared to 95 clinical isolates recently obtained in Austrian hospitals. Ten water samples were taken from four main rivers, collected upstream and downstream of major cities in 2016. For subtyping and comparison, public core genome multi locus sequence typing (cgMLST) schemes were used. The presence of AMR genes, virulence genes and plasmids was extracted from whole genome sequence (WGS) data. In total three ESBL-producing strains and two carbapenem resistant strains were isolated. WGS based comparison of these five water isolates to 95 clinical isolates identified three clusters. Cluster 1 (ST11) and cluster 2 (ST985) consisted of doublets of carbapenem resistant strains (one water and one clinical isolate each). Cluster 3 (ST405) consisted of three ESBL-producing strains isolated from one water sample and two clinical specimens. The cities, in which patient isolates of cluster 2 and 3 were collected, were in concordance with the water sampling locations downstream from these cities. The genetic concordance between isolates from river water samples and patient isolates raises concerns regarding the release of wastewater treatment plant effluents into surface water. From a public health perspective these findings demand attention and strategies are required to minimize the spread of multiresistant strains to the environment.
Published: 2019

20. Between a rock and a soft place: the role of viruses in lithification of modern microbial mats

Author: Pieter T. Visscher, Richard A. White, Brendan P. Burns, Plant Pathology, Washington State University (WSU), Australian Centre for Astrobiology, University of New South Wales [Sydney] (UNSW), RAW Molecular Systems LLC, Departments of Marine Sciences & Geosciences, University of Connecticut (UCONN), Biogéosciences [UMR 6282] [Dijon] (BGS), Centre National de la Recherche Scientifique (CNRS)-Université de Bourgogne (UB)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement, School of Biotechnology and Biomolecular Sciences, and National Science Foundation (Division of Ocean Sciences) grant 1561173.
Subjects: Microbiology (medical), Geologic Sediments, Biogeochemical cycle, viral lifestyle, Earth science, virus–host interactions, Geologic record, Microbiology, MESH: Host-Parasite Interactions, Host-Parasite Interactions, MESH: Viruses, 03 medical and health sciences, Geologic time scale, bacteriophage, Virology, lytic/lysogenic cycle, viruses, Microbial mat, stromatolite, Lithification, 030304 developmental biology, early Earth, 0303 health sciences, Bacteria, biology, 030306 microbiology, MESH: Virus Physiological Phenomena, microbialites, Biosphere, exopolymeric substances (EPS), MESH: Geologic Sediments, biology.organism_classification, Early Earth, microbial mat, MESH: Bacteria, Infectious Diseases, [SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology, Stromatolite, 13. Climate action, CRISPR, biosignatures, Virus Physiological Phenomena
Abstract: 10 pages; International audience; Stromatolites are geobiological systems formed by complex microbial communities, and fossilized stromatolites provide a record of some of the oldest life on Earth. Microbial mats are precursors of extant stromatolites; however, the mechanisms of transition from mat to stromatolite are controversial and are still not well understood. To fully recognize the profound impact that these ecosystems have had on the evolution of the biosphere requires an understanding of modern lithification mechanisms and how they relate to the geological record. We propose here viral mechanisms in carbonate precipitation, leading to stromatolite formation, whereby viruses directly or indirectly impact microbial metabolisms that govern the transition from microbial mat to stromatolite. Finding a tangible link between host-virus interactions and changes in biogeochemical processes will provide tools to interpret mineral biosignatures through geologic time, including those on Earth and beyond.
Published: 2021

21. Nested structure of intraspecific competition network in Carnobacterium maltaromaticum

Author: Ramia, Nancy E., Mangavel, Cécile, Gaiani, Claire, Muller-Gueudin, Aurélie, Taha, Samir, Revol-Junelles, Anne-Marie, Borges, Frédéric, Laboratoire d'Ingénierie des Biomolécules (LIBio), Université de Lorraine (UL), Laboratoire de Biotechnologies Appliquées, Université Libanaise, Institut Élie Cartan de Lorraine (IECL), Université de Lorraine (UL)-Centre National de la Recherche Scientifique (CNRS), Biology, genetics and statistics (BIGS), Inria Nancy - Grand Est, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria)-Institut Élie Cartan de Lorraine (IECL), and Université de Lorraine (UL)-Centre National de la Recherche Scientifique (CNRS)-Université de Lorraine (UL)-Centre National de la Recherche Scientifique (CNRS)
Subjects: MESH: Microbial ecology, [SDV]Life Sciences [q-bio], lcsh:Medicine, Food Contamination, Microbial Sensitivity Tests, [SDV.BID]Life Sciences [q-bio]/Biodiversity, Binding, Competitive, Article, Microbial ecology, [SDV.EE.ECO]Life Sciences [q-bio]/Ecology, environment/Ecosystems, Bacteriocins, Species Specificity, Antibiosis, Fish Products, Animals, Humans, Lactic Acid, lcsh:Science, [SDV.GEN]Life Sciences [q-bio]/Genetics, Bacteria, lcsh:R, Fishes, Listeria monocytogenes, Meat Products, MESH: Bacteria, Food Microbiology, Carnobacterium, lcsh:Q, [SDV.EE.IEO]Life Sciences [q-bio]/Ecology, environment/Symbiosis
Abstract: International audience; While competition targeting food-borne pathogens is being widely documented, few studies have focused on competition among non-pathogenic food bacteria. Carnobacterium maltaromaticum is a genetically diverse lactic acid bacterium known for comprising several bacteriocinogenic strains with bioprotective potentialities against the food-borne pathogen Listeria monocytogenes. The aim of our study is to examine the network properties of competition among a collection of 73 strains of C. maltaromaticum and to characterize their individual interaction potential. The performed high-throughput competition assays, investigating 5 329 pairwise interactions, showed that intraspecific competition was major in C. maltaromaticum with approximately 56% of the sender strains antagonizing at least one receiver strain. A high diversity of inhibitory and sensitivity spectra was identified along with a majority of narrow inhibitory as well as sensitivity spectra. Through network analysis approach, we determined the highly nested architecture of C. maltaromaticum competition network, thus showing that competition in this species is determined by both the spectrum width of the inhibitory activity of sender strains and the spectrum width of the sensitivity of receiver strains. This study provides knowledge of the competition network in C. maltaromaticum that could be used in rational assembly of compatible microbial strains for the design of mixed starter cultures.
Published: 2020

22. No evidence of Phago-mixotropy in Micromonas polaris (Mamiellophyceae), the Dominant Picophytoplankton Species in the Arctic

Author: John A. Burns, Fabrice Not, Florence Le Gall, Daniel Vaulot, Valeria Jimenez, Adaptation et diversité en milieu marin (AD2M), 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)-Centre National de la Recherche Scientifique (CNRS), ECOlogy of MArine Plankton (ECOMAP), Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS)-Station biologique de Roscoff (SBR), Bigelow Laboratory for Ocean Sciences, and Nanyang Technological University [Singapour]
Subjects: 0106 biological sciences, [SDV]Life Sciences [q-bio], MESH: Arctic Regions, Zoology, Plant Science, Aquatic Science, 010603 evolutionary biology, 01 natural sciences, MESH: Chlorophyta, Ochromonas, Arctic, Polaris, Chlorophyta, Phytoplankton, Micromonas, phago-mixotrophy, biology, Bacteria, Arctic Regions, 010604 marine biology & hydrobiology, biology.organism_classification, The arctic, Phago, MESH: Bacteria, phytoplankton, Seasons, MESH: Seasons, geographic locations
Abstract: International audience; In the Arctic Ocean, the small green alga Micromonas polaris dominates picophytoplankton during the summer months but is also present in winter. It has been previously hypothesized to be phago-mixotrophic (capable of bacteria ingestion) based on laboratory and field experiments. Prey uptake was analyzed in several M. polaris strains isolated from different regions and depths of the Arctic Ocean and in Ochromonas triangulata, a known phago-mixotroph used as a control. Measuring ingestion of either fluorescent beads or fluorescently labeled bacteria by flow cytometry, we found no evidence of phago-mixotrophy in any M. polaris strain while O. triangulata was ingesting both beads and bacteria. In addition, in silico predictions revealed that members of the genus Micromonas lack a genetic signature of phagocytotic capacity.
Published: 2020

23. Genome-wide analysis of the Firmicutes illuminates the diderm/monoderm transition

Author: Jerzy Witwinowski, Simonetta Gribaldo, Guillaume Borrel, Panagiotis S. Adam, Daniela Megrian, Najwa Taib, Christophe Beloin, Daniel Poppleton, Biologie Evolutive de la Cellule Microbienne - Evolutionary Biology of the Microbial Cell, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Hub Bioinformatique et Biostatistique - Bioinformatics and Biostatistics HUB, Collège doctoral [Sorbonne universités], Sorbonne Université (SU), Génétique des Biofilms - Genetics of Biofilms, S.G., C.B. and J.W. acknowledge funding from the French National Research Agency (ANR), project Fir-OM (grant no. ANR-16-CE12-0010) and from the Institut Pasteur Programmes Transversaux de Recherche (grant no. PTR 39–16). D.M. and D.P. were supported by the Pasteur-Paris University (PPU) International PhD Program. This work used the computational and storage services (TARS cluster) provided by the IT department at Institut Pasteur, Paris., ANR-16-CE12-0010,Fir-OM,Firmicutes avec une membrane externe: vers des nouveaux modeles d'étude de la transition monodermes/didermes(2016), Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), and Collège Doctoral
Subjects: Firmicutes, Chemie, Gram-Positive Bacteria, Genome, MESH: Gram-Positive Bacteria, 03 medical and health sciences, Gram-Negative Bacteria, MESH: Gram-Negative Bacteria, Humans, Clade, MESH: Phylogeny, MESH: Firmicutes, Ecology, Evolution, Behavior and Systematics, Phylogeny, 030304 developmental biology, 0303 health sciences, Halanaerobiales, Negativicutes, MESH: Humans, Ecology, Phylogenetic tree, biology, Bacteria, 030306 microbiology, Phylum, biology.organism_classification, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, MESH: Bacteria, Evolutionary biology, Bacterial outer membrane
Abstract: Phylogenomic analysis supports a diderm ancestor of the Firmicutes and points to an early origin of two-membraned cells in Bacteria and the derived nature of the Gram-positive envelope following multiple outer membrane losses. The transition between cell envelopes with one membrane (Gram-positive or monoderm) and those with two membranes (Gram-negative or diderm) is a fundamental open question in the evolution of Bacteria. Evidence of the presence of two independent diderm lineages, the Halanaerobiales and the Negativicutes, within the classically monoderm Firmicutes has blurred the monoderm/diderm divide and specifically anticipated that other members with an outer membrane (OM) might exist in this phylum. Here, by screening 1,639 genomes of uncultured Firmicutes for signatures of an OM, we highlight a third and deep branching diderm clade, the Limnochordia, strengthening the hypothesis of a diderm ancestor and the occurrence of independent transitions leading to the monoderm phenotype. Phyletic patterns of over 176,000 protein families constituting the Firmicutes pan-proteome identify those that strongly correlate with the diderm phenotype and suggest the existence of new potential players in OM biogenesis. In contrast, we find practically no largely conserved core of monoderms, a fact possibly linked to different ways of adapting to repeated OM losses. Phylogenetic analysis of a concatenation of main OM components totalling nearly 2,000 amino acid positions illustrates the common origin and vertical evolution of most diderm bacterial envelopes. Finally, mapping the presence/absence of OM markers onto the tree of Bacteria shows the overwhelming presence of diderm phyla and the non-monophyly of monoderm ones, pointing to an early origin of two-membraned cells and the derived nature of the Gram-positive envelope following multiple OM losses.
Published: 2020

24. Microbial dark matter filling the niche in hypersaline microbial mats

Author: Pieter T. Visscher, Brendan P. Burns, Richard A. White, Hon Lun Wong, Fraser I. MacLeod, School of Biotechnology and Biomolecular Sciences, University of New South Wales [Sydney] (UNSW), Australian Centre for Astrobiology, RAW Molecular Systems LLC, Departments of Marine Sciences and Geoscience, University of Connecticut (UCONN), Biogéosciences [UMR 6282] [Dijon] (BGS), and Centre National de la Recherche Scientifique (CNRS)-Université de Bourgogne (UB)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement
Subjects: Microbiology (medical), Salinity, Microorganism, Niche, MESH: Australia, Microbiology, lcsh:Microbial ecology, 03 medical and health sciences, Microbial ecology, Dissimilatory sulfate reduction, MESH: Ecosystem, Ecosystem, Microbial mat, 030304 developmental biology, 0303 health sciences, Bacteria, biology, 030306 microbiology, Phylum, Ecology, Research, RuBisCO, Australia, MESH: Metagenome, biology.organism_classification, Archaea, MESH: Bacteria, [SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology, MESH: Archaea, biology.protein, lcsh:QR100-130, Metagenome, Eukaryote, MESH: Salinity
Abstract: Background Shark Bay, Australia, harbours one of the most extensive and diverse systems of living microbial mats that are proposed to be analogs of some of the earliest ecosystems on Earth. These ecosystems have been shown to possess a substantial abundance of uncultivable microorganisms. These enigmatic microbes, jointly coined as ‘microbial dark matter’ (MDM), are hypothesised to play key roles in modern microbial mats. Results We reconstructed 115 metagenome-assembled genomes (MAGs) affiliated to MDM, spanning 42 phyla. This study reports for the first time novel microorganisms (Zixibacterial order GN15) putatively taking part in dissimilatory sulfate reduction in surface hypersaline settings, as well as novel eukaryote signature proteins in the Asgard archaea. Despite possessing reduced-size genomes, the MDM MAGs are capable of fermenting and degrading organic carbon, suggesting a role in recycling organic carbon. Several forms of RuBisCo were identified, allowing putative CO2 incorporation into nucleotide salvaging pathways, which may act as an alternative carbon and phosphorus source. High capacity of hydrogen production was found among Shark Bay MDM. Putative schizorhodopsins were also identified in Parcubacteria, Asgard archaea, DPANN archaea, and Bathyarchaeota, allowing these members to potentially capture light energy. Diversity-generating retroelements were prominent in DPANN archaea that likely facilitate the adaptation to a dynamic, host-dependent lifestyle. Conclusions This is the first study to reconstruct and describe in detail metagenome-assembled genomes (MAGs) affiliated with microbial dark matter in hypersaline microbial mats. Our data suggests that these microbial groups are major players in these systems. In light of our findings, we propose H2, ribose and CO/CO2 as the main energy currencies of the MDM community in these mat systems.
Published: 2020

25. Evidence for contamination as the origin for bacteria found in human placenta rather than a microbiota

Author: Sandra Wydau-Dematteis, Sean Kennedy, Rémi Gschwind, Vassilis Tsatsaris, Anne-Gaël Cordier, Marie-José Butel, Frédéric Barbut, Thierry Fournier, Physiopathologie et pharmacotoxicologie placentaire humaine : Microbiote pré & post natal (3PHM - UMR-S 1139), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), PremUp Foundation, Institut de Recherche pour le Développement (IRD)-CHI Créteil-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université Paris-Saclay-Université Paris Cité (UPCité), Département de Biologie Computationnelle - Department of Computational Biology, Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), This work was supported by a PRIDE grant from the hospital-university department 'Risks in Pregnancy' and by Paris Descartes university., and Kennedy, Sean
Subjects: 0301 basic medicine, Embryology, Placenta, Extraembryonic Membranes, Physiology, Umbilical cord, Umbilical Cord, Database and Informatics Methods, 0302 clinical medicine, MESH: Pregnancy, Pregnancy, Medicine and Health Sciences, MESH: Chorionic Villi, DNA extraction, reproductive and urinary physiology, 030219 obstetrics & reproductive medicine, Multidisciplinary, medicine.diagnostic_test, Microbiota, Genomics, MESH: Cesarean Section, MESH: Placenta, MESH: Chorionic Villi Sampling, medicine.anatomical_structure, [SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology, Chorionic Villi Sampling, Obstetric Procedures, Medical Microbiology, In utero, embryonic structures, Chorionic villi, Medicine, Female, Chorionic Villi, Sequence Analysis, Research Article, Adult, DNA, Bacterial, Bioinformatics, Science, Sequence Databases, Chorionic villus sampling, Surgical and Invasive Medical Procedures, Microbial Genomics, Biology, Microbiology, Specimen Handling, 03 medical and health sciences, Extraction techniques, Genetics, medicine, Humans, MESH: Microbiota, Microbiome, MESH: Specimen Handling, [SDV.MP] Life Sciences [q-bio]/Microbiology and Parasitology, Fetus, MESH: Humans, Bacteria, MESH: Umbilical Cord, Cesarean Section, MESH: Extraembryonic Membranes, Gut Bacteria, Organisms, Biology and Life Sciences, MESH: Adult, Delivery, Obstetric, medicine.disease, MESH: DNA, Bacterial, Research and analysis methods, MESH: Bacteria, Biological Databases, 030104 developmental biology, MESH: Delivery, Obstetric, Metagenomics, MESH: Female, Developmental Biology
Abstract: International audience; Until recently the in utero environment of pregnant women was considered sterile. Recent high-sensitivity molecular techniques and high-throughput sequencing lead to some evidence for a low-biomass microbiome associated with the healthy placenta. Other studies failed to reveal evidence for a consistent presence of bacteria using either culture or molecular based techniques. Comparing conflicting "placental microbiome" studies is complicated by the use of varied and inconsistent protocols. Given this situation, we undertook an evaluation of the in utero environment sterility using several controlled methods, in the same study, to evaluate the presence or absence of bacteria and to explain contradictions present in the literature. Healthy pregnant women (n = 38) were recruited in three maternity wards. Placenta were collected after cesarean section with or without Alexis ® and vaginal delivery births. For this study we sampled fetal membranes, umbilical cord and chorionic villi. Bacterial presence was analyzed using bacterial culture and qPCR on 34 fetal membranes, umbilical cord and chorionic villi samples. Shotgun metagenomics was performed on seven chorionic villi samples. We showed that the isolation of meaningful quantities of viable bacteria or bacterial DNA was possible only outside the placenta (fetal membranes and umbilical cords) highlighting the importance of sampling methods in studying the in utero environment. Bacterial communities described by metagenomics analysis were similar in chorionic villi samples and in negative controls and were dependent on the database chosen for the analysis. We conclude that the placenta does not harbor a specific, consistent and functional microbiota.
Published: 2020

26. A synthesis of bacterial and archaeal phenotypic trait data

Author: Ross Corkrey, David Danko, Joshua S. Madin, T. B. K. Reddy, Mark Westoby, Sara Vieira-Silva, Thomas M. Schmidt, Eduardo P. C. Rocha, Martin K. M. Engqvist, Matthew A. Richards, Noah Fierer, Lisa R. Moore, Alice R. Wattam, Fran Supek, Maria Brbic, Heba Shaaban, Michael R. Gillings, Christopher E. Mason, David A. Westfall, Nikos C. Kyrpides, Daniel A. Nielsen, Maulik Shukla, Elena Litchman, Kyle F. Edwards, Jemma L. Geoghegan, Sasha G. Tetu, Søren Laurentius Nielsen, Nathan D. Price, Ian T. Paulsen, University of Hawai‘i [Mānoa] (UHM), Macquarie University [Sydney], Rudjer Boskovic Institute [Zagreb], University of Tasmania [Hobart, Australia] (UTAS), Weill Cornell Medicine [New York], Chalmers University of Technology [Gothenburg, Sweden], University of Colorado [Boulder], Lawrence Berkeley National Laboratory [Berkeley] (LBNL), Michigan State University [East Lansing], Michigan State University System, Roskilde University, Institute for Systems Biology [Seattle] (ISB), Génomique évolutive des Microbes / Microbial Evolutionary Genomics, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), University of Michigan [Ann Arbor], University of Michigan System, Argonne National Laboratory [Lemont] (ANL), Institute for Research in Biomedicine [Barcelona, Spain] (IRB), University of Barcelona-Barcelona Institute of Science and Technology (BIST), Rega Institute for Medical Research [Leuven, België], Catholic University of Leuven - Katholieke Universiteit Leuven (KU Leuven), University of Virginia [Charlottesville], Weill Cornell Medicine [Cornell University], Cornell University [New York], Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), and University of Virginia
Subjects: Statistics and Probability, Data Descriptor, MESH: Genome, Archaeal, Library and Information Sciences, MESH: Genome, Bacterial, MESH: Phenotype, Genome, Education, Microbial ecology, 03 medical and health sciences, Genome, Archaeal, Abundance (ecology), [SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], Genetics, Ecosystem, MESH: Ecosystem, lcsh:Science, 030304 developmental biology, 0303 health sciences, [SDV.GEN.GPO]Life Sciences [q-bio]/Genetics/Populations and Evolution [q-bio.PE], biology, Bacteria, 030306 microbiology, [SDV.BID.EVO]Life Sciences [q-bio]/Biodiversity/Populations and Evolution [q-bio.PE], Human Genome, Bacterial, Phenotypic trait, biology.organism_classification, Phenotype, Archaea, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, [SDV.BIBS]Life Sciences [q-bio]/Quantitative Methods [q-bio.QM], Computer Science Applications, MESH: Bacteria, Habitat, Evolutionary biology, Archaeal, MESH: Archaea, Trait, lcsh:Q, Statistics, Probability and Uncertainty, [INFO.INFO-BI]Computer Science [cs]/Bioinformatics [q-bio.QM], Genome, Bacterial, Information Systems, Biotechnology
Abstract: A synthesis of phenotypic and quantitative genomic traits is provided for bacteria and archaea, in the form of a scripted, reproducible workflow that standardizes and merges 26 sources. The resulting unified dataset covers 14 phenotypic traits, 5 quantitative genomic traits, and 4 environmental characteristics for approximately 170,000 strain-level and 15,000 species-aggregated records. It spans all habitats including soils, marine and fresh waters and sediments, host-associated and thermal. Trait data can find use in clarifying major dimensions of ecological strategy variation across species. They can also be used in conjunction with species and abundance sampling to characterize trait mixtures in communities and responses of traits along environmental gradients., Measurement(s)Trait • phenotypic trait • quantitative genomic traitTechnology Type(s)digital curationFactor Type(s)habitat • speciesSample Characteristic - OrganismArchaea • BacteriaSample Characteristic - Locationglobal Machine-accessible metadata file describing the reported data: 10.6084/m9.figshare.12221732
Published: 2020

27. Customizing Host Chromatin

Author: Michael Connor, Laurence Arbibe, Mélanie Hamon, Chromatine et Infection, Institut Pasteur [Paris], Chromatine et Infection - Chromatin and Infection, Institut Necker Enfants-Malades (INEM - UM 111 (UMR 8253 / U1151)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP), 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), and ANR-16-CE15-0006,EPI-CURE,Le régulateur épigénétique HP1 dans la tolérance intestinale et les maladies inflammatoires intestinales chroniques: fonctions et potentiel thérapeutique(2016)
Subjects: MESH: Cell Nucleus, MESH: Histones, MESH: Humans, MESH: Bacterial Infections, MESH: Host-Pathogen Interactions, MESH: DNA, [SDV.BBM.BM]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology, [SDV.BC.BC]Life Sciences [q-bio]/Cellular Biology/Subcellular Processes [q-bio.SC], [SDV.BC]Life Sciences [q-bio]/Cellular Biology, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, MESH: Chromatin, MESH: Bacteria, MESH: DNA Methylation, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, ComputingMilieux_MISCELLANEOUS
Abstract: International audience; Chromatin is located within the nuclei of eukaryotic cells and is composed of DNA wrapped around histone proteins. The highly ordered compaction of chromatin is crucial for the different functions encoded by the genetic material. These range from maintaining cell identity and genome integrity to adapting to environmental stimuli and cell replication. At the center of the chromatin language is its structural organization. This depends on the position and reversible covalent modifications to histone proteins and their cross talk with DNA and regulatory proteins. The basic unit of chromatin is the nucleosome, which is composed of an octamer of four histone proteins (H2A, H2B, H3, and H4) around which ∼147 bases of DNA are wrapped, with the linker histone (H1) outside the core structure providing structural integrity to the complex. Nucleosome remodelers are ATP-dependent enzymes that modify the chromatin structure through translocation, eviction, and introduction of histone variants ( 1 , 2 ), while histone-modifying enzymes introduce reversible covalent posttranslational modifications (PTMs) to histone tails.
Published: 2020

28. Natural variation in physicochemical profiles and bacterial communities associated with Aedes aegypti breeding sites and larvae on Guadeloupe and French Guiana

Author: Lyza Hery, Josiann Normandeau-Guimond, Philippe Constant, Joël Gustave, Isabelle Dusfour, Daniella Goindin, Christelle Delannay, Stéphanie Raffestin, Jean Issaly, Claude Guertin, Sébastien Breurec, Audrey-Anne Durand, Yann Reynaud, Anubis Vega-Rúa, Amandine Guidez, Grégory Legrave, Unité Transmission, Réservoir et Diversité des Pathogènes [Pasteur Guadeloupe, France] (TReD-Path), Institut Pasteur de la Guadeloupe, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP), Vectopôle Amazonien Emile Abonnenc [Cayenne, Guyane française], Institut Pasteur de la Guyane, Institut Armand Frappier (INRS-IAF), Institut National de la Recherche Scientifique [Québec] (INRS)-Réseau International des Instituts Pasteur (RIIP), Laboratoire d’Hygiène de l’Environnement [Institut Pasteur de Guadeloupe] (LHE), Agence régionale de santé Guadeloupe (ARS), Laboratoire Hygiène et Environnement [Institut Pasteur de la Guyane] (LHE), Université des Antilles - UFR des sciences médicales Hyacinthe Bastaraud (UA UFR SM), Université des Antilles (UA), Centre d'Investigation Clinique Antilles-Guyane (CIC - Antilles Guyane), CHU de Fort de France-Centre Hospitalier Andrée Rosemon [Cayenne, Guyane Française]-CHU Pointe-à-Pitre/Abymes [Guadeloupe] -Institut National de la Santé et de la Recherche Médicale (INSERM)-Université des Antilles et de la Guyane (UAG), This work was supported by Action Concertées Inter Pasteuriennes (Grant ACIP 01-2016) and by the Programme Opérationnel FEDER-Guadeloupe-Conseil Régional 2014–2020 (grant 2015-FED-192). LH was funded by a PhD scholarship from La Région Guadeloupe and her missions were supported by the Calmette & Yersin program from the Institut Pasteur Department of International Affairs., and Courcelles, Michel
Subjects: animal structures, [SDV]Life Sciences [q-bio], Microorganism, Soil Science, Zoology, Mosquito Vectors, Aedes aegypti, Microbial ecology, Aedes, RNA, Ribosomal, 16S, parasitic diseases, MESH: French Guiana, MESH: Water, Environmental Microbiology, MESH: Guadeloupe, MESH: Microbiota, Animals, MESH: Animals, Guadeloupe, Relative species abundance, Ecology, Evolution, Behavior and Systematics, Abiotic component, Physicochemical parameter, Larva, Bacteria, Ecology, biology, Microbiota, Aquatic ecosystem, fungi, Breeding site, Water, MESH: Aedes, biology.organism_classification, French Guiana, MESH: RNA, Ribosomal, 16S, [SDV] Life Sciences [q-bio], MESH: Bacteria, MESH: Mosquito Vectors, Ordination, Bacterial community, MESH: Larva
Abstract: Background: Immature stages of Aedes aegypti develop in many man-made aquatic habitats in which mosquito larvae are exposed to physicochemical elements and microorganisms that may influence their life cycle and their ability to transmit human arboviruses. Despite the omnipresence of Ae. aegypti in tropical and subtropical regions, little is known about the natural bacterial communities associated with this mosquito or their relation to the biotic and abiotic characteristics of their aquatic habitats. We comprehensively characterized the physicochemical properties and bacterial microbiome of Ae. aegypti breeding sites and larvae on Guadeloupe and in French Guiana. In addition, we explored whether geographical location, the type of breeding site and physicochemical parameters of the water influenced the microbiota associated with this mosquito species.Method: We used large-scale 16S rRNA gene sequencing of 160 breeding sites and 147 pools of Ae. aegypti larvae from sites widely distributed across Guadeloupe and French Guiana and recorded 13 physicochemical parameters at the sampled breeding sites. Ordination plots and multiple linear regression were used to assess the influence of environmental factors on the bacterial microbiome of water and larvae.Results: We found territory-specific differences in physicochemical properties (dissolved oxygen, conductivity and metal content) and the composition of bacterial communities in Ae. aegypti breeding sites that influenced the relative abundance of several bacteria genera (Methylobacterium, Roseoccocus) on the corresponding larvae. A significant fraction of the bacterial communities identified on Ae. aegypti larvae, dominated by Herbiconiux and Microvirga genera, were consistently enriched in mosquitoes regardless the location. Conclusion: Territory-specific differences observed in the biotic and abiotic properties of Ae. aegypti breeding sites influenced a fraction of the microbial communities of the corresponding larvae, raising concern about the impact of these changes on pathogen transmission by different Ae. aegypti populations.
Published: 2020

29. Usefulness of à la carte antigens for bird fancier’s lung serodiagnosis: total dropping extract and/or dropping’s microflora antigens

Author: Sandrine Roussel, Audrey Laboissière, Benoît Valot, Jean-Charles Dalphin, Adeline Rouzet, Paul De Vuyst, Gabriel Reboux, Laurence Millon, Laboratoire Chrono-environnement ( LCE ), Université Bourgogne Franche-Comté ( UBFC ) -Centre National de la Recherche Scientifique ( CNRS ) -Université de Franche-Comté ( UFC ), Service de parasitologie et mycologie [CHU de Besançon], Centre Hospitalier Régional Universitaire [Besançon] ( CHRU Besançon ), Service de Pneumologie, Hôpital Jean-Minjoz, Centre Hospitalier Universitaire de Besançon, Université de Franche-Comté, Besançon, France., Erasme Hospital, Brussels, Hôpital Jean Minjoz, Laboratoire Chrono-environnement - CNRS - UBFC (UMR 6249) (LCE), Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC)-Centre National de la Recherche Scientifique (CNRS), Service de parasitologie et mycologie [CHRU de Besançon], Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Service de Pneumologie, oncologie thoracique et allergologie respiratoire [CHRU Besançon], Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), Hôpital Erasme [Bruxelles] (ULB), Faculté de Médecine [Bruxelles] (ULB), and Université libre de Bruxelles (ULB)-Université libre de Bruxelles (ULB)
Subjects: diagnosis, MESH : Antigens, serology, Serology, Feces, 0302 clinical medicine, Bird fancier's lung, antigens, Flora (microbiology), MESH : Bird Fancier's Lung, MESH: Animals, 030212 general & internal medicine, microorganisms, MESH: Bird Fancier's Lung, MESH : Allergens, Immunoassay, biology, MESH: Feces, General Medicine, Enterobacter, MESH : Immunoassay, MESH : Serologic Tests, 3. Good health, medicine.anatomical_structure, MESH: Birds, MESH: Antigens, Antibody, medicine.symptom, MESH: Immunoassay, MESH: Fungi, Microbiology (medical), MESH: Allergens, droppings, Microbiology, Asymptomatic, [ SDV.EE.SANT ] Life Sciences [q-bio]/Ecology, environment/Health, Birds, 03 medical and health sciences, Antigen, medicine, Animals, Humans, Serologic Tests, MESH : Bacteria, MESH : Birds, MESH : Fungi, bird fancier's lung, [SDV.EE.SANT]Life Sciences [q-bio]/Ecology, environment/Health, MESH: Humans, Lung, Bacteria, MESH: Serologic Tests, MESH : Humans, Fungi, MESH : Feces, Allergens, medicine.disease, biology.organism_classification, MESH: Bacteria, 030228 respiratory system, Immunology, biology.protein, MESH : Animals, [ SDV.MHEP.PSR ] Life Sciences [q-bio]/Human health and pathology/Pulmonology and respiratory tract
Abstract: International audience; Bird fancier's lung (BFL) is a pulmonary disease caused by inhalation of avian proteins. The involvement of the microorganisms of droppings has been assumed in the past and this idea still persists today. Our study aimed to compare by immunoprecipitation assay the detection of antibodies against both droppings and microorganisms in the sera of patients (n=15) and asymptomatic exposed controls (n=18). We found that 14/15 BFL patients had negative serological results for isolated microorganisms of the droppings, only one positive against Enterobacter sakasakii. Serological arguments were in accordance with diagnosis in 87 % of cases by testing à la carte antigens from each bird dropping versus 20 % using the standard antigenic panel. Otherwise, the microorganisms antigens issued from dropping flora were negative in 93 % of cases. Consequently, it's preferable to use the total extract from the patient's bird droppings to establish the serodiagnosis of the disease.
Published: 2017

30. Versatile modes of cellular regulation via cyclic dinucleotides

Author: Holger Sondermann, Petya V. Krasteva, Biologie Structurale de la Sécrétion Bactérienne, Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), 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), Cornell University [New York], Work in the Sondermann laboratory is supported by US National Institutes of Health grant R01-AI097307 (H.S.). P.V.K. is supported by the Centre National de la Recherche Scientifique (CNRS) and the Institute for Integrative Biology of the Cell (I2BC) and was previously a recipient of a Roux-Cantarini postdoctoral fellowship from the Institut Pasteur., Centre National de la Recherche Scientifique (CNRS)-Institut Pasteur [Paris], and Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS)
Subjects: Models, Molecular, 0301 basic medicine, Cell signaling, [SDV]Life Sciences [q-bio], 030106 microbiology, Chemical biology, MESH: Amino Acid Sequence, Computational biology, Biology, Article, 03 medical and health sciences, Animals, Humans, MESH: Animals, Amino Acid Sequence, Biofilm formation, Molecular Biology, MESH: Prokaryotic Cells, MESH: Humans, Bacteria, Effector, Cellular Regulation, Eukaryota, c-di-GMP, Cell Biology, Physiological responses, Cell biology, MESH: Bacteria, MESH: Eukaryota, MESH: Nucleotides, Cyclic, 030104 developmental biology, Prokaryotic Cells, Structural biology, MESH: Protein Processing, Post-Translational, Second messenger system, dinucleotide signaling, Nucleotides, Cyclic, Protein Processing, Post-Translational, MESH: Models, Molecular, Cyclic dinucleotides
Abstract: International audience; Since the discovery of c-di-GMP almost three decades ago, cyclic dinucleotides (CDNs) have emerged as widely used signaling molecules in most kingdoms of life. The family of second messengers now includes c-di-AMP and distinct versions of mixed cyclic GMP-AMP (cGAMP) compounds. In addition to these nucleotides, a vast number of proteins for the production and turnover of these molecules have been described, as well as effectors that translate the signals into physiological responses. The latter include, but are not limited to, mechanisms for adaptation and survival in prokaryotes, persistence and virulence of bacterial pathogens, and immune responses to viral and bacterial invasion in eukaryotes. In this review, we will focus on recent discoveries and emerging themes that illustrate the ubiquity and versatility of cyclic dinucleotide function at the transcriptional and post-translational levels and, in particular, on insights gained through mechanistic structure-function analyses.
Published: 2017

31. The use of genomic DNA sequences as type material for valid publication of bacterial species names will have severe implications for clinical microbiology and related disciplines

Author: Magne Bisgaard, J. Michael Janda, Niels Nørskov-Lauritsen, Henrik Christensen, Alexandr Nemec, Dominique Clermont, Frans A. G. Reubsaet, Jörg Overmann, Edward R. B. Moore, Lenie Dijkshoorn, Bisgaard Consulting, Faculty of Health and Medical Sciences, University of Copenhagen = Københavns Universitet (KU), Collection de l'Institut Pasteur (CIP), Institut Pasteur [Paris], Leiden University Medical Center (LUMC), Kern County Public Health Laboratory [Bakersfield], University of Gothenburg (GU), Laboratory of Bacterial Genetics, National Institute of Public Health, Department of Clinical Microbiology, Aarhus University Hospital, Leibniz-Institut DSMZ-Deutsche Sammlung von Mikroorganismen und Zellkulturen GmbH / Leibniz Institute DSMZ-German Collection of Microorganisms and Cell Cultures (DSMZ), German Center for Infection Research - partner site Hannover-Braunschweig (DZIF), Braunschweig University of Technology, National Institute of Public Health and the Environment (NIPHE), University of Copenhagen = Københavns Universitet (UCPH), Institut Pasteur [Paris] (IP), and Universiteit Leiden
Subjects: DNA, Bacterial, Microbiology (medical), MESH: Terminology as Topic, MESH: Bacterial Infections, [SDV]Life Sciences [q-bio], Computational biology, Biology, MESH: Genome, Bacterial, 03 medical and health sciences, Type (biology), Terminology as Topic, MESH: Publishing, ComputingMilieux_MISCELLANEOUS, 030304 developmental biology, Publishing, 0303 health sciences, Bacteria, 030306 microbiology, Bacterial Infections, General Medicine, MESH: DNA, Bacterial, 3. Good health, genomic DNA, Clinical microbiology, MESH: Bacteria, Infectious Diseases, [SDE]Environmental Sciences, Genome, Bacterial
Abstract: International audience
Published: 2019

32. Epidemiology and Appropriateness of Antibiotic Prescribing in Severe Pneumonia After Lung Resection

Author: Anne Casetta, Yên-Lan Nguyen, Samir Bouam, Rémy Gauzit, Aurélie Lefebvre, Antoine Rabbat, Julien Caliez, Kim Blanc, E. Canouï, Jean-François Regnard, Solen Kernéis, Marco Alifano, J. Loubinoux, Université Paris Descartes - Paris 5 (UPD5), Biostatistique, Biomathématique, Pharmacoépidémiologie et Maladies Infectieuses (B2PHI), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), and Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: Male, [SDV]Life Sciences [q-bio], 030204 cardiovascular system & hematology, Antimicrobial Stewardship, Postoperative Complications, 0302 clinical medicine, MESH: Aged, 80 and over, MESH: Postoperative Complications, Epidemiology, Antimicrobial stewardship, Pneumonectomy, Aged, 80 and over, MESH: Aged, MESH: Middle Aged, Incidence (epidemiology), Mortality rate, Middle Aged, Anti-Bacterial Agents, 3. Good health, Female, Cardiology and Cardiovascular Medicine, Empiric therapy, Adult, Pulmonary and Respiratory Medicine, medicine.medical_specialty, MESH: Pneumonia, Bacterial, 03 medical and health sciences, Internal medicine, MESH: Anti-Bacterial Agents, Drug Resistance, Bacterial, MESH: Drug Resistance, Bacterial, Pneumonia, Bacterial, medicine, Humans, MESH: Antimicrobial Stewardship, Aged, Retrospective Studies, MESH: Humans, Bacteria, business.industry, MESH: Pneumonectomy, Retrospective cohort study, MESH: Adult, MESH: Retrospective Studies, Guideline, medicine.disease, MESH: Male, Pneumonia, MESH: Bacteria, 030228 respiratory system, Surgery, business, MESH: Female
Abstract: International audience; Background: Postoperative pneumonia (POP) is a severe complication of major lung resection. The objective of this study was to describe the current epidemiology and appropriateness of antibiotic prescriptions in severe POP, 4 years after implementation of an antimicrobial stewardship program that was based on weekly multidisciplinary review of all antibiotic therapies.Methods: This study was a retrospective analysis of a prospectively collected database. It included all cases of severe POP occurring within 30 days after major lung resection of in a 1,500-bed hospital between 2013 and 2015. Criteria for severe POP were acute respiratory failure, severe sepsis, or a rapidly extensive pulmonary infiltrate. The study collected data on incidence, clinical outcomes, and microbiological analyses. Appropriateness of antibiotic prescribing was assessed by quality indicators previously validated in the literature.Results: Over the study period, 1,555 patients underwent major lung surgery. Severe POP occurred in 91 patients (5.8%; confidence interval, 4.7%; 7.0%), with a mortality rate of 9.0% (8 of 91; confidence interval, 3.0%; 14.6%). In POP with positive microbiological results, the proportion of gram-negative bacteria other than Haemophilus was 76% (50 of 66 cases). All patients (91 of 91) had respiratory samples taken within 24 hours after the start of antibiotics; empiric therapy was concordant with the guideline in 80% (69 of 86), and it was switched to pathogen-directed therapy in 74% (46 of 62). In 71 of 91 patients (78%), the antibiotic duration was up to 7 days.Conclusions: This study reported a high proportion of gram-negative bacteria in severe POP. Four years after implementation of the program, quality indicators of antibiotic prescribing were all >70%. The rate of de-escalation to pathogen-directed therapy could be improved, however.
Published: 2019

33. Estimating the division rate from indirect measurements of single cells

Author: Lydia Robert, Adélaïde Olivier, Marie Doumic, Modelling and Analysis for Medical and Biological Applications (MAMBA), Inria de Paris, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria)-Laboratoire Jacques-Louis Lions (LJLL (UMR_7598)), Université Paris Diderot - Paris 7 (UPD7)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Diderot - Paris 7 (UPD7)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Sorbonne Université (SU), Université Paris-Sud 11 - Faculté des Sciences (UP11 UFR Sciences), Université Paris-Sud - Paris 11 (UP11), MICrobiologie de l'ALImentation au Service de la Santé (MICALIS), Institut National de la Recherche Agronomique (INRA)-AgroParisTech, Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Université Paris-Sud - Paris 11 - Faculté des Sciences (UP11 UFR Sciences), AgroParisTech-Université Paris-Saclay-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), European Project: 306321,EC:FP7:ERC,ERC-2012-StG_20111012,SKIPPERAD(2012), and Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP)
Subjects: Adder, eigenvalue problems, Kernel density estimation, Population, Mathematics - Statistics Theory, Statistics Theory (math.ST), MSC: 35R30, 92B05, 35Q62, 62G30, 45Q05, 01 natural sciences, Adder model, Mathematics - Analysis of PDEs, [MATH.MATH-ST]Mathematics [math]/Statistics [math.ST], FOS: Mathematics, Discrete Mathematics and Combinatorics, Applied mathematics, [MATH.MATH-AP]Mathematics [math]/Analysis of PDEs [math.AP], 0101 mathematics, education, Mathematics, Variable (mathematics), cell division cycle, education.field_of_study, inverse problems, Applied Mathematics, 010102 general mathematics, Probability (math.PR), nonparametric estimation, [STAT.TH]Statistics [stat]/Statistics Theory [stat.TH], Division (mathematics), Inverse problem, 010101 applied mathematics, [MATH.MATH-PR]Mathematics [math]/Probability [math.PR], incremental model, Trait, MESH: bacteria, Incremental build model, MESH: cell cycle, kernel density estimation, Mathematics - Probability, Analysis of PDEs (math.AP)
Abstract: International audience; Is it possible to estimate the dependence of a growing and dividing population on a given trait in the case where this trait is not directly accessible by experimental measurements, but making use of measurements of another variable? This article adresses this general question for a very recent and popular model describing bacterial growth, the so-called incremental or adder model. In this model, the division rate depends on the increment of size between birth and division, whereas the most accessible trait is the size itself. We prove that estimating the division 10 rate from size measurements is possible, we state a reconstruction formula in a deterministic and then in a statistical setting, and solve numerically the problem on simulated and experimental data. Though this represents a severely ill-posed inverse problem, our numerical results prove to be satisfactory.
Published: 2019

34. The Many Faces of Bacterium-Endothelium Interactions during Systemic Infections

Author: Guillaume Duménil, Dorian Obino, Pathogénèse des Infections vasculaires / Pathogenesis of Vascular Infections, Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Pascale Cossart, Craig R. Roy, Philippe Sansonetti, Lassailly-Bondaz, Anne, Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM), and Obino, Dorian
Subjects: Microbiology (medical), [SDV.MHEP.AHA] Life Sciences [q-bio]/Human health and pathology/Tissues and Organs [q-bio.TO], Endothelium, Physiology, MESH: Bacterial Infections, Inflammation, Drug resistance, 030204 cardiovascular system & hematology, Biology, MESH: Endothelium, medicine.disease_cause, 03 medical and health sciences, 0302 clinical medicine, Antibiotic resistance, Intensive care, Drug Resistance, Bacterial, MESH: Drug Resistance, Bacterial, Genetics, medicine, [SDV.MHEP.AHA]Life Sciences [q-bio]/Human health and pathology/Tissues and Organs [q-bio.TO], Animals, Humans, MESH: Animals, Organism, 030304 developmental biology, 0303 health sciences, MESH: Humans, General Immunology and Microbiology, Ecology, Bacteria, 030306 microbiology, Neisseria meningitidis, MESH: Host-Pathogen Interactions, Cell Biology, Bacterial Infections, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, 3. Good health, Endothelial stem cell, MESH: Bacteria, Infectious Diseases, medicine.anatomical_structure, Immunology, Host-Pathogen Interactions, cardiovascular system, Endothelium, Vascular, MESH: Endothelium, Vascular, medicine.symptom, [SDV.MP.BAC] Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology
Abstract: Voir aussi le même article publié dans le livre : https://onlinelibrary.wiley.com/doi/book/10.1128/9781683670261 ; Dépôt : https://hal-pasteur.archives-ouvertes.fr/pasteur-03116237; International audience; The endothelium is the layer of endothelial cells lining the inner surface of blood vessels, which span the entire body and ensure the distribution of blood throughout the organism. It is estimated that the human body contains a staggering 100,000 km of blood vessels, more than twice the earth’s circumference. Therefore, a bacterium reaching the circulation is engaged in a network of huge proportions. Moreover, a pathogen traveling through the circulatory system does not encounter a homogeneous environment, as an important feature of the vascular network is its diversity. Although endothelial cells are present in all vessels, the organization of the vessel wall, which is formed by three layers—the tunica intima, media, and adventitia (from the vessel lumen outward)—is different among different vessel types and different organs. Vessels can be first differentiated by the complex extracellular matrix layers surrounding them. For instance, elastic arteries such as the aorta are surrounded by 50 elastic layers, providing them with unique mechanical properties. Second, the cellular content is also different according to vessel type; the walls of arteries and veins contain a layer of smooth muscle cells that gives them the capacity to relax or constrict in response to vasoactive molecules. An additional level of complexity in the network stems from the fact that larger vessels, veins or arteries, are themselves vascularized by smaller vessels, the vasa vasorum.
Published: 2019

35. An updated structural classification of replicative DNA polymerases

Author: Pierre Raia, Marc Delarue, Ludovic Sauguet, Dynamique structurale des Macromolécules / Structural Dynamics of Macromolecules, Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Sorbonne Université (SU), ANR-17-CE11-0005,ARCHAPOL,Spécificités structurales et potentiel biotechnologique de la PolD, une ADN polymérase atypique d'archée(2017), and Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS)
Subjects: DNA polymerase, Protein Conformation, MESH: Biological Evolution, MESH: DNA Replication, DNA-Directed DNA Polymerase, DNA replication, Biochemistry, Genome, 03 medical and health sciences, DNA polymerases, 0302 clinical medicine, MESH: Protein Conformation, proofreading, evolution, MESH: DNA-Directed DNA Polymerase, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, Polymerase, 030304 developmental biology, Genetics, 0303 health sciences, biology, Bacteria, Eukaryota, Processivity, biology.organism_classification, Archaea, Biological Evolution, genomic DNA, MESH: Bacteria, MESH: Eukaryota, classification, MESH: Archaea, biology.protein, Proofreading, PolD, 030217 neurology & neurosurgery
Abstract: Replicative DNA polymerases are nano-machines essential to life, which have evolved the ability to copy the genome with high fidelity and high processivity. In contrast with cellular transcriptases and ribosome machines, which evolved by accretion of complexity from a conserved catalytic core, no replicative DNA polymerase is universally conserved. Strikingly, four different families of DNA polymerases have evolved to perform DNA replication in the three domains of life. In Bacteria, the genome is replicated by DNA polymerases belonging to the A- and C-families. In Eukarya, genomic DNA is copied mainly by three distinct replicative DNA polymerases, Polα, Polδ, and Polε, which all belong to the B-family. Matters are more complicated in Archaea, which contain an unusual D-family DNA polymerase (PolD) in addition to PolB, a B-family replicative DNA polymerase that is homologous to the eukaryotic ones. PolD is a heterodimeric DNA polymerase present in all Archaea discovered so far, except Crenarchaea. While PolD is an essential replicative DNA polymerase, it is often underrepresented in the literature when the diversity of DNA polymerases is discussed. Recent structural studies have shown that the structures of both polymerase and proofreading active sites of PolD differ from other structurally characterized DNA polymerases, thereby extending the repertoire of folds known to perform DNA replication. This review aims to provide an updated structural classification of all replicative DNAPs and discuss their evolutionary relationships, both regarding the DNA polymerase and proofreading active sites.
Published: 2019

36. The Battle Within: Interactions of Bacteriophages and Bacteria in the Gastrointestinal Tract

Author: Luisa De Sordi, Laurent Debarbieux, Marta Lourenço, Département de Microbiologie - Department of Microbiology, Institut Pasteur [Paris], Centre de Recherche Saint-Antoine (CR Saint-Antoine), Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Saint-Antoine [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), Collège doctoral [Sorbonne universités], Sorbonne Université (SU), Institut Carnot Pasteur Maladie Infectieuse ANR-11-CARN-017-01, M.L. is part of the Pasteur- Paris University (PPU) International PhD Program and has received funding from the Institut Carnot Pasteur Maladie Infectieuse (ANR 11-CARN 017- 01). L.D.S. is funded by a Roux-Cantarini fellowship from the Institut Pasteur (Paris, France). L.D. received support from the DigestScience Foundation (Lille, France)., Cova Rodrigues, Ana, Institut Pasteur [Paris] (IP), 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), and Collège Doctoral
Subjects: [SDV]Life Sciences [q-bio], Intestinal physiology, In silico, Microbiology, MESH: Gastrointestinal Microbiome, Biological Coevolution, 03 medical and health sciences, Human health, Mice, 0302 clinical medicine, Virology, MESH: Biological Coevolution, Animals, Humans, MESH: Animals, Bacteriophages, MESH: Bacteriophages, MESH: Mice, Coevolution, 030304 developmental biology, Genetics, 0303 health sciences, Gastrointestinal tract, MESH: Humans, biology, Bacteria, Healthy subjects, biology.organism_classification, Gastrointestinal Microbiome, Specific Pathogen-Free Organisms, [SDV] Life Sciences [q-bio], MESH: Microbial Interactions, MESH: Specific Pathogen-Free Organisms, Gastrointestinal Tract, MESH: Bacteria, Microbial Interactions, MESH: Gastrointestinal Tract, Parasitology, 030217 neurology & neurosurgery
Abstract: International audience; The intestinal microbiota is intimately linked to human health. Decoding the mechanisms underlying its stability in healthy subjects should uncover causes of microbiota-associated diseases and pave the way for treatment. Bacteria and bacteriophages (phages) are the most abundant biological entities in the gastrointestinal tract, where their coexistence is dynamic and affixed. Phages drive and maintain bacterial diversity by perpetuating the coevolutionary interactions with their microbial prey. This review brings together recent in silico, in vitro, and in vivo work dissecting the complexity of phage-bacteria interactions in the intestinal microbiota, including coevolution perspectives. We define the types of dynamics encountered in the gastrointestinal tract and the parameters that affect their outcome. The impact of intestinal physiology on phagebacterial coevolution is analyzed in the light of its potential contribution to the relationship between the microbiota and human health.
Published: 2019

37. Penicillin-Binding Proteins (PBPs) and Bacterial Cell Wall Elongation Complexes

Author: Andréa Dessen, Mayara M. Miyachiro, Carlos Contreras-Martel, Brazilian Biosciences National Laboratory (LNBio), National Center for Research in Energy and Materials, Institut de biologie structurale (IBS - UMR 5075 ), Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), 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)-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 National de la Recherche Scientifique (CNRS), Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), and ANR-18-CE11-0019,PSEUDO-WALL,Architecture et fonction de complexes de la biosynthèse de la paroi cellulaire de Pseudomonas aeruginosa(2018)
Subjects: Penicillin binding proteins, Protein complexes, Peptidoglycan, Bacterial cell structure, Cell wall, 03 medical and health sciences, chemistry.chemical_compound, MESH: Cell Wall, Membrane proteins, medicine, Penicillin-Binding proteins (PBPs), Cell wall elongation, 030304 developmental biology, 0303 health sciences, MESH: Penicillin-Binding Proteins, [SDV.BBM.BS]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Structural Biology [q-bio.BM], 030306 microbiology, MESH: Peptidoglycan, Periplasmic space, Cell biology, Penicillin, MESH: Bacteria, chemistry, Membrane protein, Structural biology, Periplasm, medicine.drug
Abstract: International audience; The bacterial cell wall is the validated target of mainstream antimicrobials such as penicillin and vancomycin. Penicillin and other β-lactams act by targeting Penicillin-Binding Proteins (PBPs), enzymes that play key roles in the biosynthesis of the main component of the cell wall, the peptidoglycan. Despite the spread of resistance towards these drugs, the bacterial cell wall continues to be a major Achilles' heel for microbial survival, and the exploration of the cell wall formation machinery is a vast field of work that can lead to the development of novel exciting therapies. The sheer complexity of the cell wall formation process, however, has created a significant challenge for the study of the macromolecular interactions that regulate peptidoglycan biosynthesis. New developments in genetic and biochemical screens, as well as different aspects of structural biology, have shed new light on the importance of complexes formed by PBPs, notably within the cell wall elongation machinery. This chapter summarizes structural and functional details of PBP complexes involved in the periplasmic and membrane steps of peptidoglycan biosynthesis with a focus on cell wall elongation. These assemblies could represent interesting new targets for the eventual development of original antibacterials.
Published: 2019

38. Art and microbiology: encounters of the third type

Author: Frédéric Barras, Adaptation au stress et métabolisme chez les entérobactéries - Stress adaptation and metabolism in enterobacteria, Institut Pasteur [Paris], Institut Pasteur, ANR et CNRS, I am grateful to Regine Hengge (Berlin) and Mathias Springer (Paris) for their support and help with the manuscript. Thanks are due to S. Bäumel (Amsterdam, NL), M. Berkmen (New England Biolabs, Ipswich), M.L. Bernardini and R. Di Leonardo (Università della Sapienza, Roma) C. Marizzi (Cold Spring Harbor Lab, New York), G. Ranalli (Pisa), C. Ward (New York), for generous gift of photo of their work. Part of this manuscript was written on a leave in Prof. B. Colonna's laboratory at Università della Sapienza, Roma., and Institut Pasteur [Paris] (IP)
Subjects: 0301 basic medicine, MESH: Humans, Bacteria, media_common.quotation_subject, 030106 microbiology, Art, [SHS.ART]Humanities and Social Sciences/Art and art history, Bacterial Physiological Phenomena, Art & Science, Microbiology, Agricultural and Biological Sciences (miscellaneous), World Wide Web, 03 medical and health sciences, MESH: Bacteria, Type (biology), [SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology, MESH: Bacterial Physiological Phenomena, MESH: Microbiology, MESH: Biotechnology, Humans, Ecology, Evolution, Behavior and Systematics, ComputingMilieux_MISCELLANEOUS, Biotechnology, media_common
Abstract: International audience
Published: 2018

39. New lipophilic glycomimetic DC-SIGN ligands: Stereoselective synthesis and SPR-based binding inhibition assays

Author: Mauro Pineschi, Paolo Crotti, Dalila Iacopini, Franck Fieschi, Vittorio Bordoni, Silvia Achilli, Valeria Di Bussolo, Michel Thépaut, Sebastiano Di Pietro, Dipartimento di Farmacia, University of Pisa - Università di Pisa, Dipartimento Farm, Dipartimento di Chimica e Chimica Industriale, Institut de biologie structurale (IBS - UMR 5075), Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), 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)-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 Grenoble Alpes (UGA), Dipartimento Chim & Chim Ind, and ANR-17-EURE-0003,CBH-EUR-GS,CBH-EUR-GS(2017)
Subjects: Disaccharide, Mannose, Disaccharides, Ligands, 01 natural sciences, Biochemistry, Fucose, chemistry.chemical_compound, Glycomimetic, MESH: Disaccharides, Drug Discovery, MESH: Ligands, Moiety, MESH: Receptors, Cell Surface, [SDV.BBM.BS]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Structural Biology [q-bio.BM], biology, Stereoisomerism, Stereoselectivity, Anti-Bacterial Agents, MESH: Surface Plasmon Resonance, DC-SIGN, MESH: Cell Adhesion Molecules, Anti-infective agents, Protein Binding, MESH: Antiviral Agents, Lipophilic interactions, Stereochemistry, Carbohydrates, Receptors, Cell Surface, Antiviral Agents, MESH: Anti-Bacterial Agents, Humans, MESH: Protein Binding, Lectins, C-Type, Molecular Biology, MESH: Humans, Bacteria, 010405 organic chemistry, Ligand, Organic Chemistry, Surface Plasmon Resonance, MESH: Stereoisomerism, 0104 chemical sciences, Glycomimetics, MESH: Bacteria, 010404 medicinal & biomolecular chemistry, chemistry, biology.protein, Azide, Cell Adhesion Molecules, MESH: Lectins, C-Type
Abstract: International audience; The design and synthesis of efficient ligands for DC-SIGN is a topic of high interest, because this C-type lectin has been implicated in the early stages of many infection processes. DC-SIGN membrane-protein presents four carbohydrate-binding domains (CRD) that specifically recognize mannose and fucose. Therefore, antagonists of minimal disaccharide epitope Manα(1,2)Man, represent potentially interesting antibacterial and antiviral agents. In the recent past, we were able to develop efficient antagonists, mimics of the natural moiety, characterized by the presence of a real d-carbamannose unit which confers greater stability to enzymatic breakdown than the corresponding natural disaccharide ligand. Herein, we present the challenging stereoselective synthesis of four new amino or azide glycomimetic DC-SIGN antagonists with attractive orthogonal lipophilic substituents in C(3), C(4) or C(6) positions of the real carba unit, which were expected to establish crucial interactions with lipophilic areas of DC-SIGN CRD. The activity of the new ligands was evaluated by SPR binding inhibition assays. The interesting results obtained, allow to acquire important information about the influence of the lipophilic substituents present in specific positions of the carba scaffold. Furthermore, C(6) benzyl C(4) tosylamide pseudodisaccharide displayed a good affinity for DC-SIGN with a more favorable IC50 value than those of the previously described real carba-analogues. This study provides valuable knowledge for the implementation of further structural modifications towards improved inhibitors.
Published: 2021

40. Control of fluxes in metabolic networks

Author: Yang-Yu Liu, Abdelhalim Larhlimi, Georg Basler, Albert-László Barabási, Zoran Nikoloski, Combinatoire et Bioinformatique (COMBI), Laboratoire des Sciences du Numérique de Nantes (LS2N), IMT Atlantique Bretagne-Pays de la Loire (IMT Atlantique), Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT)-Université de Nantes - UFR des Sciences et des Techniques (UN UFR ST), Université de Nantes (UN)-Université de Nantes (UN)-École Centrale de Nantes (ECN)-Centre National de la Recherche Scientifique (CNRS)-IMT Atlantique Bretagne-Pays de la Loire (IMT Atlantique), Université de Nantes (UN)-Université de Nantes (UN)-École Centrale de Nantes (ECN)-Centre National de la Recherche Scientifique (CNRS), Université de Nantes - UFR des Sciences et des Techniques (UN UFR ST), and Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT)
Subjects: MESH: Signal Transduction, MESH: Fungi, [INFO.INFO-CC]Computer Science [cs]/Computational Complexity [cs.CC], 0301 basic medicine, Gene regulatory network, Method, Computational biology, [INFO.INFO-DM]Computer Science [cs]/Discrete Mathematics [cs.DM], Biology, Models, Biological, [INFO.INFO-AI]Computer Science [cs]/Artificial Intelligence [cs.AI], Evolution, Molecular, 03 medical and health sciences, 0302 clinical medicine, [INFO.INFO-LG]Computer Science [cs]/Machine Learning [cs.LG], Genetics, Animals, Humans, MESH: Animals, Gene Regulatory Networks, Control (linguistics), MESH: Evolution, Molecular, Genetics (clinical), MESH: Gene Regulatory Networks, Regulation of gene expression, MESH: Humans, Bacteria, Extramural, Cellular Regulation, MESH: Models, Biological, Fungi, Computational Biology, MESH: Gene Expression Regulation, [SDV.BIBS]Life Sciences [q-bio]/Quantitative Methods [q-bio.QM], 3. Good health, MESH: Bacteria, Multicellular organism, 030104 developmental biology, Gene Expression Regulation, MESH: Metabolic Networks and Pathways, 030220 oncology & carcinogenesis, Metabolic Networks and Pathways, Human cancer, MESH: Computational Biology, Signal Transduction
Abstract: Understanding the control of large-scale metabolic networks is central to biology and medicine. However, existing approaches either require specifying a cellular objective or can only be used for small networks. We introduce new coupling types describing the relations between reaction activities, and develop an efficient computational framework, which does not require any cellular objective for systematic studies of large-scale metabolism. We identify the driver reactions facilitating control of 23 metabolic networks from all kingdoms of life. We find that unicellular organisms require a smaller degree of control than multicellular organisms. Driver reactions are under complex cellular regulation in Escherichia coli, indicating their preeminent role in facilitating cellular control. In human cancer cells, driver reactions play pivotal roles in malignancy and represent potential therapeutic targets. The developed framework helps us gain insights into regulatory principles of diseases and facilitates design of engineering strategies at the interface of gene regulation, signaling, and metabolism.
Published: 2016

41. Are Bacteria Infectious Pathogens in Hidradenitis Suppurativa? Debate at the Symposium for Hidradenitis Suppurativa Advances Meeting, November 2017

Author: Michelle A. Lowes, Mayur Ramesh, Gregory S. Schultz, Vincent Piguet, Aude Nassif, Haley B. Naik, Afsaneh Alavi, University of California [San Francisco] (UCSF), University of California, Centre Médical de l'Institut Pasteur (CMIP), Institut Pasteur [Paris], Centre d'infectiologie Necker-Pasteur [CHU Necker], Institut Pasteur [Paris]-CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), University of Toronto, Rockefeller University [New York], University of California [San Francisco] (UC San Francisco), University of California (UC), Institut Pasteur [Paris] (IP), Institut Pasteur [Paris] (IP)-CHU Necker - Enfants Malades [AP-HP], and Centre Médical de l'Institut Pasteur
Subjects: 0301 basic medicine, [SDV]Life Sciences [q-bio], Dermatology, MESH: Hidradenitis Suppurativa, Biochemistry, Article, 03 medical and health sciences, 0302 clinical medicine, MESH: Microbiota, Medicine, Humans, Hidradenitis suppurativa, Molecular Biology, Retrospective Studies, MESH: Humans, biology, Bacteria, business.industry, Microbiota, MESH: Retrospective Studies, Cell Biology, Congresses as Topic, medicine.disease, biology.organism_classification, Hidradenitis Suppurativa, MESH: Bacteria, 030104 developmental biology, Infectious disease (medical specialty), 030220 oncology & carcinogenesis, Immunology, business, MESH: Congresses as Topic, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, [SDV.MHEP.DERM]Life Sciences [q-bio]/Human health and pathology/Dermatology
Abstract: Meeting held at Henry Ford Hospital, Detroit, Michigan, in November 2017; International audience; In November 2017, a formal debate on the role of bacteria in the pathogenesis of hidradenitis suppurativa (HS) was held at the 2nd Symposium on Hidradenitis Suppurativa Advances (SHSA) in Detroit, Michigan. In this report, we present both sides of the argument as debated at the SHSA meeting and then discuss the potential role of bacteria as classic infectious pathogens versus an alternative pathogenic role as activators of dysregulated commensal bacterial-host interactions. Although there was consensus that bacteria play a role in pathogenesis and thus are pathogenic, there was a compelling discussion about whether bacteria in HS incite an infectious disease as we classically understand it or whether bacteria might play a different role in HS pathogenesis.
Published: 2018

42. Supervised machine learning outperforms taxonomy-based environmental DNA metabarcoding applied to biomonitoring

Author: Thorsten Stoeck, Catarina I. M. Martins, Tristan Cordier, Yoann Dufresne, Dominik Forster, Jan Pawlowski, Department of genetics and evolution, Université de Genève = University of Geneva (UNIGE), University of Kaiserslautern [Kaiserslautern], Hub Bioinformatique et Biostatistique - Bioinformatics and Biostatistics HUB, Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Swiss Network for International Studies. Grant Number: 316030_150817 Swiss National Science Foundation. Grant Number: 31003A_179125 Deutsche Forschungsgemeinschaft. Grant Number: STO414/15-1 Carl Zeiss Foundation NVIDIA GPU grant program, University of Geneva [Switzerland], and Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS)
Subjects: 0301 basic medicine, computer.software_genre, chemistry.chemical_compound, Molecular marker, Biomonitoring, Environmental DNA, supervised machine learning, Independent data, Eukaryota, Biodiversity, predictive models, MESH: Eukaryota, MESH: Supervised Machine Learning, Taxonomy (biology), MESH: Metagenomics, MESH: Environmental Monitoring, Biotechnology, Environmental Monitoring, Biology, Machine learning, MESH: Biodiversity, 03 medical and health sciences, MESH: Computer Simulation, Genetics, DNA Barcoding, Taxonomic, Computer Simulation, 14. Life underwater, MESH: DNA Barcoding, Taxonomic, Ecology, Evolution, Behavior and Systematics, Bacteria, business.industry, Marine aquaculture, Significant difference, biotic indices, environmental DNA, MESH: Bacteria, 030104 developmental biology, chemistry, RNA, Ribosomal, biomonitoring, MESH: Biomarkers, MESH: RNA, Ribosomal, Artificial intelligence, Metagenomics, [INFO.INFO-BI]Computer Science [cs]/Bioinformatics [q-bio.QM], [SDE.BE]Environmental Sciences/Biodiversity and Ecology, business, Bioindicator, computer, Biomarkers
Abstract: International audience; Biodiversity monitoring is the standard for environmental impact assessment of anthropogenic activities. Several recent studies showed that high-throughput amplicon sequencing of environmental DNA (eDNA metabarcoding) could overcome many limitations of the traditional morphotaxonomy-based bioassessment. Recently, we demonstrated that supervised machine learning (SML) can be used to predict accurate biotic indices values from eDNA metabarcoding data, regardless of the taxonomic affiliation of the sequences. However, it is unknown to which extent the accuracy of such models depends on taxonomic resolution of molecular markers or how SML compares with metabarcoding approaches targeting well-established bioindicator species. In this study, we address these issues by training predictive models upon five different ribosomal bacterial and eukaryotic markers and measuring their performance to assess the environmental impact of marine aquaculture on independent data sets. Our results show that all tested markers are yielding accurate predictive models and that they all outperform the assessment relying solely on taxonomically assigned sequences. Remarkably, we did not find any significant difference in the performance of the models built using universal eukaryotic or prokaryotic markers. Using any molecular marker with a taxonomic range broad enough to comprise different potential bioindicator taxa, SML approach can overcome the limits of taxonomy-based eDNA bioassessment.
Published: 2018

43. Genomic insights into the emergence and spread of antimicrobial-resistant bacterial pathogens

Author: Kathryn E. Holt, Stephen Baker, François-Xavier Weill, Nicholas R. Thomson, Oxford University Clinical Research Unit [Ho Chi Minh City] (OUCRU), University of Oxford [Oxford], University of Cambridge [UK] (CAM), The Wellcome Trust Sanger Institute [Cambridge], London School of Hygiene and Tropical Medicine (LSHTM), Bactéries pathogènes entériques (BPE), Institut Pasteur [Paris], University of Melbourne, S.B. is a Sir Henry Dale Fellow, jointly funded by the Wellcome Trust and the Royal Society (100087/Z/12/Z). K.E.H. is a Viertel Foundation of Australia Senior Medical Research Fellow and HHMI-Gates International Research Scholar. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript., University of Oxford, Institut Pasteur [Paris] (IP), Baker, Stephen [0000-0003-1308-5755], Thomson, Nicholas [0000-0002-4432-8505], Weill, François-Xavier [0000-0001-9941-5799], Holt, Kathryn E [0000-0003-3949-2471], and Apollo - University of Cambridge Repository
Subjects: 0301 basic medicine, Methicillin-Resistant Staphylococcus aureus, 030106 microbiology, Sexually Transmitted Diseases, Genomics, Computational biology, Review, MESH: Methicillin-Resistant Staphylococcus aureus, Biology, MESH: Genome, Bacterial, Evolution, Molecular, Foodborne Diseases, 03 medical and health sciences, Antibiotic resistance, MESH: Anti-Bacterial Agents, Drug Resistance, Bacterial, MESH: Drug Resistance, Bacterial, Spatial evolution, Humans, MESH: Foodborne Diseases, MESH: Evolution, Molecular, Multidisciplinary, MESH: Humans, Bacteria, Whole Genome Sequencing, MESH: Genomics, Antimicrobial, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, 3. Good health, Anti-Bacterial Agents, Community-Acquired Infections, MESH: Bacteria, 030104 developmental biology, MESH: Community-Acquired Infections, MESH: Whole Genome Sequencing, Genome, Bacterial, MESH: Sexually Transmitted Diseases
Abstract: International audience; Whole-genome sequencing (WGS) has been vital for revealing the rapid temporal and spatial evolution of antimicrobial resistance (AMR) in bacterial pathogens. Some antimicrobial-resistant pathogens have outpaced us, with untreatable infections appearing in hospitals and the community. However, WGS has additionally provided us with enough knowledge to initiate countermeasures. Although we cannot stop bacterial adaptation, the predictability of many evolutionary processes in AMR bacteria offers us an opportunity to channel them using new control strategies. Furthermore, by using WGS for coordinating surveillance and to create a more fundamental understanding of the outcome of antimicrobial treatment and AMR mechanisms, we can use current and future antimicrobials more effectively and aim to extend their longevity.
Published: 2018

44. Editorial overview: Host–pathogen interactions shaped through evolutionary and regulatory processes

Author: Carmen Buchrieser, Joan Mecsas, Biologie des Bactéries intracellulaires - Biology of Intracellular Bacteria, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Tufts University School of Medicine [Boston], and Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS)
Subjects: Microbiology (medical), 0303 health sciences, MESH: Humans, Bacteria, 030306 microbiology, Host (biology), Microbiota, MESH: Host-Pathogen Interactions, MESH: Biological Evolution, Computational biology, Biology, Biological Evolution, Microbiology, 03 medical and health sciences, MESH: Bacteria, Infectious Diseases, [SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], Host-Pathogen Interactions, Humans, bacteria, MESH: Microbiota, Pathogen, 030304 developmental biology
Abstract: Comment on Bacterial microbiota of the nasal passages across the span of human life. [Curr Opin Microbiol. 2018] Evolution of virulence in Enterococcus faecium, a hospital-adapted opportunistic pathogen. [Curr Opin Microbiol. 2018] The challenges of integrating two genomes in one cell. [Curr Opin Microbiol. 2018]; International audience
Published: 2018

45. Cyclic di-AMP in host–pathogen interactions

Author: Patrick Trieu-Cuot, Arnaud Firon, Laura Devaux, Pierre-Alexandre Kaminski, Biologie des Bactéries pathogènes à Gram-positif, Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Université Paris Diderot - Paris 7 (UPD7), This work was supported by the LABEX program of the French government, grant number ANR-10-LABX-62-IBEID, and the Fondation pour la Recherche Médicale (FRM), grant number DEQ20130326538. Laura Devaux is the recipient of a PhD grant from the Ecole Doctorale Bio Sorbonne Paris Cité (BioSPC), Université Paris Diderot. The authors are grateful to Laura Gomez-Valero for her advice on iTOL and phylogenetics., ANR-10-LABX-0062,IBEID,Integrative Biology of Emerging Infectious Diseases(2010), and Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS)
Subjects: 0301 basic medicine, Microbiology (medical), MESH: Signal Transduction, [SDV]Life Sciences [q-bio], Human pathogen, Biology, Microbiology, 03 medical and health sciences, Mice, Interferon, medicine, Cyclic AMP, Animals, Humans, MESH: Nucleotidyltransferases, Nucleotide, MESH: Animals, Pathogen, MESH: Mice, MESH: Cyclic AMP, chemistry.chemical_classification, Innate immune system, MESH: Humans, Bacterial product, Bacteria, Host (biology), Macrophages, MESH: Host-Pathogen Interactions, Membrane Proteins, MESH: Macrophages, Nucleotidyltransferases, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, Immunity, Innate, Cell biology, Immune recognition, MESH: Bacteria, 030104 developmental biology, Infectious Diseases, [SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology, chemistry, Host-Pathogen Interactions, MESH: Immunity, Innate, MESH: Membrane Proteins, medicine.drug, Signal Transduction
Abstract: International audience; Cyclic di-AMP (c-di-AMP) is a bacterial signaling nucleotide synthesized by several human pathogens. This widespread and specific bacterial product is recognized by infected host cells to trigger an innate immune response. Detection of c-di-AMP in the host cytosol leads primarily to the induction of type I interferon via the STING-cGAS signaling axis, while being also entangled in the activation of the NF-κB pathway. During their long-standing interaction, host and pathogens have co-evolved to control c-di-AMP activation of innate immunity. On the bacterial side, the quantity of c-di-AMP released inside cells allows to manipulate the host response to exacerbate infection by avoiding immune recognition or, at the opposite, by overloading the STING-cGAS pathway.
Published: 2018

46. History of CRISPR-Cas from Encounter with a Mysterious Repeated Sequence to Genome Editing Technology

Author: Mart Krupovic, Patrick Forterre, Yoshizumi Ishino, Biologie Moléculaire du Gène chez les Extrêmophiles (BMGE), Institut Pasteur [Paris], Kyushu University [Fukuoka], 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), P.F. is supported by an ERC grant from the European Union's Seventh Framework Program (FP/2007-2013)/Project., This perspective paper stemmed from discussions during Y.I.'s stay in P.F.'s laboratory thanks to the generous support from the program of visiting researchers in Institut Pasteur and the two-country exchange program of the Japan Society for the Promotion of Science (JSPS)., We apologize to the researchers whose work was not cited due to space limitations., Institut Pasteur [Paris] (IP), and Kyushu University
Subjects: 0301 basic medicine, MESH: Gene Editing, MESH: CRISPR-Cas Systems, [SDV]Life Sciences [q-bio], 030106 microbiology, Computational biology, Biology, MESH: Genome, Bacterial, Microbiology, Genome, 03 medical and health sciences, Genome editing, repeated sequence, Escherichia coli, CRISPR, genome editing, Humans, Clustered Regularly Interspaced Short Palindromic Repeats, casposon, Repeated sequence, Molecular Biology, Gene, Sequence (medicine), Comparative genomics, Gene Editing, [SDV.GEN]Life Sciences [q-bio]/Genetics, MESH: Humans, Bacteria, MESH: Escherichia coli, MESH: Genomics, Genomics, History, 20th Century, Archaea, MESH: Bacteria, MESH: Archaea, MESH: Clustered Regularly Interspaced Short Palindromic Repeats, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, MESH: History, 20th Century, Minireview, Mobile genetic elements, CRISPR-Cas Systems, Genome, Bacterial
Abstract: Clustered regularly interspaced short palindromic repeat (CRISPR)-Cas systems are well-known acquired immunity systems that are widespread in archaea and bacteria. The RNA-guided nucleases from CRISPR-Cas systems are currently regarded as the most reliable tools for genome editing and engineering. The first hint of their existence came in 1987, when an unusual repetitive DNA sequence, which subsequently was defined as a CRISPR, was discovered in the Escherichia coli genome during an analysis of genes involved in phosphate metabolism. Similar sequence patterns were then reported in a range of other bacteria as well as in halophilic archaea, suggesting an important role for such evolutionarily conserved clusters of repeated sequences. A critical step toward functional characterization of the CRISPR-Cas systems was the recognition of a link between CRISPRs and the associated Cas proteins, which were initially hypothesized to be involved in DNA repair in hyperthermophilic archaea. Comparative genomics, structural biology, and advanced biochemistry could then work hand in hand, not only culminating in the explosion of genome editing tools based on CRISPR-Cas9 and other class II CRISPR-Cas systems but also providing insights into the origin and evolution of this system from mobile genetic elements denoted casposons. To celebrate the 30th anniversary of the discovery of CRISPR, this minireview briefly discusses the fascinating history of CRISPR-Cas systems, from the original observation of an enigmatic sequence in E. coli to genome editing in humans.
Published: 2018

47. Universal and idiosyncratic characteristic lengths in bacterial genomes

Author: Olivier Rivoire, Ivan Junier, Paul Frémont, Génomique et Évolution des Microorganismes (TIMC-IMAG-GEM), Techniques de l'Ingénierie Médicale et de la Complexité - Informatique, Mathématiques et Applications, Grenoble - UMR 5525 (TIMC-IMAG), Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), Centre interdisciplinaire de recherche en biologie (CIRB), Labex MemoLife, École normale supérieure - Paris (ENS Paris), 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 Paris), and Université Paris sciences et lettres (PSL)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: 0301 basic medicine, MESH: Chromosomes, Bacterial, MESH: Sequence Analysis, DNA, Characteristic length, Base pair, Biophysics, Bacterial genome size, MESH: Genome, Bacterial, Synteny, Genome, Evolution, Molecular, 03 medical and health sciences, 0302 clinical medicine, MESH: Base Composition, Structural Biology, Kuhn length, Quantitative Biology - Genomics, Molecular Biology, MESH: Evolution, Molecular, Genomics (q-bio.GN), Base Composition, Bacteria, Circular bacterial chromosome, [SDV.BID.EVO]Life Sciences [q-bio]/Biodiversity/Populations and Evolution [q-bio.PE], MESH: Synteny, Sequence Analysis, DNA, Cell Biology, Chromosomes, Bacterial, MESH: Bacteria, 030104 developmental biology, Evolutionary biology, FOS: Biological sciences, Genome, Bacterial, 030217 neurology & neurosurgery, GC-content
Abstract: International audience; In condensed matter physics, simplified descriptions are obtained by coarse-graining the features of a system at a certain characteristic length, defined as the typical length beyond which some properties are no longer correlated. From a physics standpoint, in vitro DNA has thus a characteristic length of 300 base pairs (bp), the Kuhn length of the molecule beyond which correlations in its orientations are typically lost. From a biology standpoint, in vivo DNA has a characteristic length of 1000 bp, the typical length of genes. Since bacteria live in very different physico-chemical conditions and since their genomes lack translational invariance, whether larger, universal characteristic lengths exist is a non-trivial question. Here, we examine this problem by leveraging the large number of fully sequenced genomes available in public databases. By analyzing GC content correlations and the evolutionary conservation of gene contexts (synteny) in hundreds of bacterial chromosomes, we conclude that a fundamental characteristic length around 10-20 kb can be defined. This characteristic length reflects elementary structures involved in the coordination of gene expression, which are present all along the genome of nearly all bacteria. Technically, reaching this conclusion required us to implement methods that are insensitive to the presence of large idiosyncratic genomic features, which may co-exist along these fundamental universal structures.
Published: 2018

48. Vast diversity of prokaryotic virus genomes encoding double jelly-roll major capsid proteins uncovered by genomic and metagenomic sequence analysis

Author: Disa Bäckström, Mart Krupovic, Eugene V. Koonin, Natalya Yutin, Thijs J. G. Ettema, National Center for Biotechnology Information (NCBI), Uppsala University, Biologie Moléculaire du Gène chez les Extrêmophiles (BMGE), Institut Pasteur [Paris] (IP), National Institutes of Health [Bethesda] (NIH), NY and EVK are supported by intramural funds of the US Department of Health and Human Services (to the National Library of Medicine). TJGE is supported by grants of the European Research Council (ERC Starting Grant 310039-PUZZLE_CELL), the Swedish Foundation for Strategic Research (SSF-FFL5) and the Swedish Research Council (VR grant 2015–04959). MK is supported by l’Agence Nationale de la Recherche (France) project ENVIRA., We acknowledge the help from chief scientist R. B. Pedersen, the scientific party and the entire crew on board the Norwegian research vessel G.O. Sars for providing marine sediment samples from the Loki’s Castle hydrothermal vent area during the summer 2010 expedition., ANR-17-CE15-0005,ENVIRA,Remodelage de la membrane cytoplasmique par les virus enveloppés d'archées(2017), European Project: 310039,EC:FP7:ERC,ERC-2012-StG_20111109,PUZZLE_CELL(2012), and Institut Pasteur [Paris]
Subjects: 0301 basic medicine, Archaeal Viruses, [SDV]Life Sciences [q-bio], Genome, MESH: Archaeal Viruses, Databases, Genetic, MESH: Genetic Variation, MESH: Phylogeny, Phylogeny, MESH: Capsid Proteins, MESH: Databases, Genetic, Genetics, MESH: Genomics, Genomics, Infectious Diseases, MESH: Archaea, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, MESH: Genome, Viral, MESH: Metagenomics, Tectiviridae, Sequence analysis, Bioinformatik och systembiologi, Genome, Viral, Biology, Microbiology, lcsh:Infectious and parasitic diseases, 03 medical and health sciences, Phylogenetics, Virology, [SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], Life Science, Human virome, lcsh:RC109-216, Gene, MESH: Tectiviridae, Bioinformatics and Systems Biology, Bacteria, Research, Genetic Variation, Archaea, Mikrobiologi, MESH: Bacteria, 030104 developmental biology, Metagenomics, Capsid Proteins
Abstract: Background Analysis of metagenomic sequences has become the principal approach for the study of the diversity of viruses. Many recent, extensive metagenomic studies on several classes of viruses have dramatically expanded the visible part of the virosphere, showing that previously undetected viruses, or those that have been considered rare, actually are important components of the global virome. Results We investigated the provenance of viruses related to tail-less bacteriophages of the family Tectiviridae by searching genomic and metagenomics sequence databases for distant homologs of the tectivirus-like Double Jelly-Roll major capsid proteins (DJR MCP). These searches resulted in the identification of numerous genomes of virus-like elements that are similar in size to tectiviruses (10–15 kilobases) and have diverse gene compositions. By comparison of the gene repertoires, the DJR MCP-encoding genomes were classified into 6 distinct groups that can be predicted to differ in reproduction strategies and host ranges. Only the DJR MCP gene that is present by design is shared by all these genomes, and most also encode a predicted DNA-packaging ATPase; the rest of the genes are present only in subgroups of this unexpectedly diverse collection of DJR MCP-encoding genomes. Only a minority encode a DNA polymerase which is a hallmark of the family Tectiviridae and the putative family "Autolykiviridae". Notably, one of the identified putative DJR MCP viruses encodes a homolog of Cas1 endonuclease, the integrase involved in CRISPR-Cas adaptation and integration of transposon-like elements called casposons. This is the first detected occurrence of Cas1 in a virus. Many of the identified elements are individual contigs flanked by inverted or direct repeats and appear to represent complete, extrachromosomal viral genomes, whereas others are flanked by bacterial genes and thus can be considered as proviruses. These contigs come from metagenomes of widely different environments, some dominated by archaea and others by bacteria, suggesting that collectively, the DJR MCP-encoding elements have a broad host range among prokaryotes. Conclusions The findings reported here greatly expand the known host range of (putative) viruses of bacteria and archaea that encode a DJR MCP. They also demonstrate the extreme diversity of genome architectures in these viruses that encode no universal proteins other than the capsid protein that was used as the marker for their identification. From a supposedly minor group of bacterial and archaeal viruses, these viruses are emerging as a substantial component of the prokaryotic virome. Electronic supplementary material The online version of this article (10.1186/s12985-018-0974-y) contains supplementary material, which is available to authorized users.
Published: 2018

49. Targeting of host organelles by pathogenic bacteria: a sophisticated subversion strategy

Author: Pedro Escoll, Carmen Buchrieser, Monica Rolando, Sonia Mondino, Biologie des Bactéries intracellulaires - Biology of Intracellular Bacteria, Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), The authors thank S. Gordon for critical reading of the manuscript. Work in the C.B. laboratory is financed by the Institut Pasteur, the Institut Carnot Pasteur Maladies Infectieuses, the French Region Ile de France (through the DIM Malinf programme) and the Infect-ERA project EUGENPATH (grant ANR-13-IFEC-0003-02). S.M. is financed by the French Agence Nationale de la Recherche (grant ANR-10-LABX- 62-IBEID). P.E. is funded by the Fondation pour la Recherche Médicale (grant DEQ20120323697)., ANR-13-IFEC-0003,EUGENPATH,Eukaryotic genes in vacuolar pathogens and symbionts - Implications for virulence, metabolism and ecology(2013), ANR-10-LABX-0062,IBEID,Integrative Biology of Emerging Infectious Diseases(2010), and Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS)
Subjects: 0301 basic medicine, MESH: Plants, [SDV.BC]Life Sciences [q-bio]/Cellular Biology, medicine.disease_cause, MESH: Eukaryotic Cells, Models, Biological, Microbiology, Bacterial genetics, 03 medical and health sciences, symbols.namesake, Bacterial secretion, Organelle, medicine, Animals, Humans, MESH: Animals, Organelles, MESH: Humans, Bacteria, General Immunology and Microbiology, biology, Host (biology), Endoplasmic reticulum, MESH: Host-Pathogen Interactions, MESH: Models, Biological, Bacterial pathogenesis, Pathogenic bacteria, Plants, Golgi apparatus, biology.organism_classification, Bacterial host response, Cell biology, MESH: Bacteria, Eukaryotic Cells, 030104 developmental biology, Infectious Diseases, Host-Pathogen Interactions, symbols, Pathogens, MESH: Organelles
Abstract: International audience; Many bacterial pathogens have evolved the ability to subvert and exploit host functions in order to enter and replicate in eukaryotic cells. For example, bacteria have developed specific mechanisms to target eukaryotic organelles such as the nucleus, the mitochondria, the endoplasmic reticulum and the Golgi apparatus. In this Review, we highlight the most recent advances in our understanding of the mechanisms that bacterial pathogens use to target these organelles. We also discuss how these strategies allow bacteria to manipulate host functions and to ultimately enable bacterial infection.
Published: 2015

50. Minimum Information about a Biosynthetic Gene cluster

Author: Patrick Caffrey, Renzo Kottmann, Eriko Takano, Sean Doyle, Axel A. Brakhage, Matthew Cummings, Juan Pablo Gomez-Escribano, Yvonne Mast, Ryan F. Seipke, Rob Lavigne, Markus Nett, Hans-Wilhelm Nützmann, Jan Claesen, David H. Sherman, Daniel Petras, Pablo Cruz-Morales, Carl J. Balibar, Anne Osbourn, Oscar P. Kuipers, Leonilde M. Moreira, Xinyu Liu, Marcia S. Osburne, Bohdan Ostash, David P. Fewer, Changsheng Zhang, Pelin Yilmaz, Mohamed S. Donia, Anja Greule, Hyun Uk Kim, Nicholas J. Tobias, Frank Oliver Glöckner, Christoph Geiger, Chia Y. Lee, William H. Gerwick, Philipp Wiemann, Bertolt Gust, Susan E. Jensen, Wilfred A. van der Donk, Jan Kormanec, Ben Shen, Christopher M. Thomas, Jason Micklefield, Srikanth Duddela, R. Cameron Coates, René De Mot, Anthony S. Haines, Neha Garg, Guohui Pan, Roderich D. Süssmuth, Hyung Jin Kwon, Jonathan D. Walton, Lena Gerwick, Jörn Piel, Monika Ehling-Schulz, Zhenhua Tian, Jonathan L. Klassen, Xiaohui Yan, Emily A. Monroe, Yunchang Xie, Russell J. Cox, Keishi Ishida, Grace Yim, Stefano Donadio, Nadine Ziemert, Yuta Tsunematsu, Matthew L. Hillwig, Miroslav Petricek, Sylvie Lautru, Tilmann Weber, Andrew W. Truman, Rainer Breitling, Peter Kötter, Nikos C. Kyrpides, Stephanie Düsterhus, Christian Hertweck, Hideaki Oikawa, Sean F. Brady, Christopher T. Walsh, Adam C. Jones, Marcus A. Moore, Bradley S. Moore, Barrie Wilkinson, Simone M. Mantovani, Nathan A. Moss, Elizabeth E. Wyckoff, Emily P. Balskus, Kapil Tahlan, Fengan Yu, Monica Höfte, Jos M. Raaijmakers, Taifo Mahmud, Yit-Heng Chooi, Yi Tang, Andreas Bechthold, Douglas A. Mitchell, Joanne M. Willey, Helge B. Bode, John B. Biggins, Margherita Sosio, Yi-Qiang Cheng, Carmen Méndez, Leonard Kaysser, Joleen Masschelein, Daniel Krug, Federico Rosconi, Marnix H. Medema, Kaarina Sivonen, Tomohisa Kuzuyama, Mikko Metsä-Ketelä, Esther K. Schmitt, Carsten Kegler, Andriy Luzhetskyy, Gilles P. van Wezel, Bai Linquan, Kai Blin, Jens Nielsen, Bertrand Aigle, Amrita Pati, Harald Gross, Muriel Viaud, Pieter C. Dorrestein, Carla S. Jones, Michael A. Fischbach, Shelley M. Payne, Zhe Rui, Gerard D. Wright, Wen Liu, Alexey V. Melnik, Barry Scott, Brett A. Neilan, Nancy P. Keller, Rainer Borriss, Katrin Jungmann, Michalis Hadjithomas, Evi Stegmann, Daniel J. Edwards, F. Jerry Reen, Alexander Kristian Apel, Wolfgang Wohlleben, Michael J. Smanski, Leonard Katz, Fergal O'Gara, Eric J. N. Helfrich, Sergey B. Zotchev, Olivier Ploux, Arnold J. M. Driessen, Rolf Müller, Jean-Luc Pernodet, K. D. Entian, José A. Salas, Irene de Bruijn, Francisco Barona-Gómez, Jianhua Ju, Jon Clardy, Molecular Microbiology, Molecular Genetics, Jacobs University [Bremen], Microbial genomics and bioinformatics research group, Max Planck Institute for Marine Microbiology, Max-Planck-Gesellschaft-Max-Planck-Gesellschaft, Max-Planck-Gesellschaft, Atmospheric Chemistry Observations and Modeling Laboratory (ACOML), National Center for Atmospheric Research [Boulder] (NCAR), Department of Food and Environmental Sciences, Helsingin yliopisto = Helsingfors universitet = University of Helsinki, Collaborative Mass Spectrometry Innovation Center, University of California [San Diego] (UC San Diego), University of California (UC)-University of California (UC), Heilongjiang Institute of Science and Technology, Eidgenössische Technische Hochschule - Swiss Federal Institute of Technology [Zürich] (ETH Zürich), Merck Stiftungsprofessur fûr Molekulare Biotechnologie Fachbereich Biowissenscharten, Goethe-University Frankfurt am Main, Department of Opto-Mechatronics Engineering and Cogno-Mechatronics Engineering, Pusan National University, University of Liverpool, College of Computer Science and Technology [Zhejiang] (Zhejiang University), University of Florida [Gainesville] (UF), School of Management, University of Science and Technology of China [Hefei] (USTC), State Key Laboratory of Nuclear Physics and Technology (SKL-NPT), Peking University [Beijing], Massachusetts Institute of Technology (MIT), Memorial Sloane Kettering Cancer Center [New York], South China Sea Institute of Oceanology, Chinese Academy of Sciences [Beijing] (CAS), Dynamique des Génomes et Adaptation Microbienne (DynAMic), Institut National de la Recherche Agronomique (INRA)-Université de Lorraine (UL), Institut für Biologie [Berlin] (IFB), Humboldt University Of Berlin, School of Biomolecular and Biomedical Science and Centre for Synthesis and Chemical Biology, University College Dublin [Dublin] (UCD), Parallélisme, Réseaux, Systèmes, Modélisation (PRISM), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Centre National de la Recherche Scientifique (CNRS), Skaggs School of Pharmacy and Pharmaceutical Sciences [San Diego], Grenoble Institut des Neurosciences (GIN), Université Joseph Fourier - Grenoble 1 (UJF)-Institut National de la Santé et de la Recherche Médicale (INSERM), Pixyl Medical [Grenoble], Integrated Optical MicroSystems (IOMS), University of Twente-MESA+ Institute for Nanotechnology, 7Lehrstuhl für Mikrobielle Ökologie, Department für Grundlagen der Biowissenschaften, Technische Universität Munchen - Université Technique de Munich [Munich, Allemagne] (TUM), Service Néphrologie Pédiatrique, CHU Strasbourg-Hôpital de Hautepierre [Strasbourg], Advanced Resources and Risk Technology, Laboratory of Phytopathology (K.C., H.S., B.A., M.H.), Universiteit Gent = Ghent University (UGENT), Trifork Aarhus C, Aalborg University [Denmark] (AAU), Centers for Disease Control and Prevention [Atlanta] (CDC), Centers for Disease Control and Prevention, Groupe d'Etude de la Matière Condensée (GEMAC), Groningen Biomolecular Sciences and Biotechnology Institute (GBB), University of Groningen [Groningen], DOE Joint Genome Institute [Walnut Creek], Microbiologie Moléculaire des Actinomycètes (ACTINO), Département Microbiologie (Dpt Microbio), 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)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)-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)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS), Institut de génétique et microbiologie [Orsay] (IGM), Université Paris-Sud - Paris 11 (UP11)-Centre National de la Recherche Scientifique (CNRS), Laboratory of Gene Technology, Catholic University of Leuven - Katholieke Universiteit Leuven (KU Leuven), Joint Center for Structural Genomics (JCSG), Stanford University, Centre européen de recherche et d'enseignement des géosciences de l'environnement (CEREGE), Institut de Recherche pour le Développement (IRD)-Institut National de la Recherche Agronomique (INRA)-Aix Marseille Université (AMU)-Collège de France (CdF (institution))-Institut national des sciences de l'Univers (INSU - CNRS)-Centre National de la Recherche Scientifique (CNRS), Centre de Recherches et d'Applications Pédagogiques en Langues (CRAPEL), Université Nancy 2, Space Sciences Laboratory [Berkeley] (SSL), University of California [Berkeley] (UC Berkeley), Polytechnic Institute of Leiria, NMR Laboratory, Université de Mons, Université de Mons (UMons), School of Biomedical Science, Curtin University [Perth], Planning and Transport Research Centre (PATREC)-Planning and Transport Research Centre (PATREC), BIOMERIT Research Centre, School of Microbiology, University College Cork (UCC), Department of Engineering Science, University of Oxford, Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS), Laboratoire Charles Friedel, Ecole Nationale Supérieure de Chimie de Paris - Chimie ParisTech-PSL (ENSCP), 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), Laboratory of Phytopathology, Wageningen University and Research [Wageningen] (WUR), Department of Microbial Ecology, Netherlands Institute of Ecology, Department of Animal Production, Universidad de Córdoba = University of Córdoba [Córdoba], IMV Technologies, Gulliver (UMR 7083), Ecole Superieure de Physique et de Chimie Industrielles de la Ville de Paris (ESPCI Paris), Institut für Chemie, Technical University of Berlin / Technische Universität Berlin (TU), Lipides - Nutrition - Cancer (U866) (LNC), Université de Bourgogne (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Ecole Nationale Supérieure de Biologie Appliquée à la Nutrition et à l'Alimentation de Dijon (ENSBANA), Centre de Recherche Paul Pascal (CRPP), Université de Bordeaux (UB)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), DEPARTMENT OF CHEMISTRY, Durham University, Molekulare Ökologie, Joint Attosecond Science Laboratory, University of Ottawa and National Research Council, Department of Mechanical and Aerospace Engineering [Univ California Davis] (MAE - UC Davis), University of California [Davis] (UC Davis), University of Helsinki, University of California-University of California, Université de Lorraine (UL)-Institut National de la Recherche Agronomique (INRA), Humboldt-Universität zu Berlin, University of Twente [Netherlands]-MESA+ Institute for Nanotechnology, Technische Universität München [München] (TUM), Universiteit Gent = Ghent University [Belgium] (UGENT), Department of Biosystems, KU Leuven, Aix Marseille Université (AMU)-Institut national des sciences de l'Univers (INSU - CNRS)-Collège de France (CdF (institution))-Institut de Recherche pour le Développement (IRD)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Recherche Agronomique (INRA), University of California [Berkeley], NMR and Molecular Imaging Laboratory [Mons], University of Mons [Belgium] (UMONS), University of Oxford [Oxford], Centre National de la Recherche Scientifique (CNRS)-Ecole Nationale Supérieure de Chimie de Paris - Chimie ParisTech-PSL (ENSCP), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut de Chimie du CNRS (INC), Universidad de Córdoba [Cordoba], Technische Universität Berlin (TU), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Bourgogne (UB)-Ecole Nationale Supérieure de Biologie Appliquée à la Nutrition et à l'Alimentation de Dijon (ENSBANA)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement, Department of Mechanical and Aerospace Engineering [Davis], Eidgenössische Technische Hochschule - Swiss Federal Institute of Technology in Zürich [Zürich] (ETH Zürich), University of Florida [Gainesville], Institut für Biologie, Humboldt Universität zu Berlin, Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Grenoble-Université Joseph Fourier - Grenoble 1 (UJF), Ghent University [Belgium] (UGENT), Université Paris-Sud - Paris 11 (UP11)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS)-Université Paris-Saclay-Université Paris-Sud - Paris 11 (UP11)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS)-Université Paris-Saclay-Institut de Biologie Intégrative de la Cellule (I2BC), Université Paris-Sud - Paris 11 (UP11)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS)-Université Paris-Saclay-Université Paris-Sud - Paris 11 (UP11)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS)-Université Paris-Saclay, Stanford University [Stanford], Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Collège de France (CdF)-Institut national des sciences de l'Univers (INSU - CNRS)-Aix Marseille Université (AMU)-Institut National de la Recherche Agronomique (INRA), NMR and Molecular Imaging Laboratory, Université Paris-Sud - Paris 11 (UP11)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS)-Université Paris-Saclay, Ecole Nationale Supérieure de Chimie de Paris- Chimie ParisTech-PSL (ENSCP)-Centre National de la Recherche Scientifique (CNRS), Wageningen University and Research Centre [Wageningen] (WUR), Gulliver, ESPCI ParisTech-Centre National de la Recherche Scientifique (CNRS), Technische Universität Berlin (TUB), Université de Bordeaux (UB)-Centre National de la Recherche Scientifique (CNRS), Max Planck Society (GERMANY), Max Planck Society (GERMANY)-Max Planck Society (GERMANY), Laboratoire Leprince-Ringuet ( LLR ), Institut National de Physique Nucléaire et de Physique des Particules du CNRS ( IN2P3 ) -École polytechnique ( X ) -Centre National de la Recherche Scientifique ( CNRS ), Atmospheric Chemistry Observations and Modeling Laboratory ( ACOML ), National Center for Atmospheric Research [Boulder] ( NCAR ), University of California [San Diego] ( UC San Diego ), Eidgenössische Technische Hochschule [Zürich] ( ETH Zürich ), University of Science and Technology of China [Hefei] ( USTC ), State Key Laboratory of Nuclear Physics and Technology ( SKL-NPT ), Massachusetts Institute of Technology ( MIT ), Memorial Sloan Kettering Cancer Center ( MSKCC ), Shanghai Ocean University, Dynamique des Génomes et Adaptation Microbienne ( DynAMic ), Institut National de la Recherche Agronomique ( INRA ) -Université de Lorraine ( UL ), University College Dublin [Dublin] ( UCD ), Parallélisme, Réseaux, Systèmes, Modélisation ( PRISM ), Université de Versailles Saint-Quentin-en-Yvelines ( UVSQ ) -Centre National de la Recherche Scientifique ( CNRS ), Grenoble Institut des Neurosciences ( GIN ), Institut National de la Santé et de la Recherche Médicale ( INSERM ) -CHU Grenoble-Université Joseph Fourier - Grenoble 1 ( UJF ), Integrated Optical MicroSystems ( IOMS ), Technische Universität München [München] ( TUM ), Ghent University [Belgium] ( UGENT ), Aalborg University [Denmark] ( AAU ), Centers for Disease Control and Prevention [Atlanta] ( CDC ), Groupe d'Etude de la Matière Condensée ( GEMAC ), Groningen Biomolecular Sciences and Biotechnology Institute ( GBB ), Microbiologie Moléculaire des Actinomycètes ( ACTINO ), Département Microbiologie ( Dpt Microbio ), Institut de Biologie Intégrative de la Cellule ( I2BC ), Université Paris-Sud - Paris 11 ( UP11 ) -Commissariat à l'énergie atomique et aux énergies alternatives ( CEA ) -Université Paris-Saclay-Centre National de la Recherche Scientifique ( CNRS ) -Université Paris-Sud - Paris 11 ( UP11 ) -Commissariat à l'énergie atomique et aux énergies alternatives ( CEA ) -Université Paris-Saclay-Centre National de la Recherche Scientifique ( CNRS ) -Institut de Biologie Intégrative de la Cellule ( I2BC ), Université Paris-Sud - Paris 11 ( UP11 ) -Commissariat à l'énergie atomique et aux énergies alternatives ( CEA ) -Université Paris-Saclay-Centre National de la Recherche Scientifique ( CNRS ) -Université Paris-Sud - Paris 11 ( UP11 ) -Commissariat à l'énergie atomique et aux énergies alternatives ( CEA ) -Université Paris-Saclay-Centre National de la Recherche Scientifique ( CNRS ), Institut de génétique et microbiologie [Orsay] ( IGM ), Université Paris-Sud - Paris 11 ( UP11 ) -Centre National de la Recherche Scientifique ( CNRS ), Joint Center for Structural Genomics ( JCSG ), Centre européen de recherche et d'enseignement de géosciences de l'environnement ( CEREGE ), Centre National de la Recherche Scientifique ( CNRS ) -Institut de Recherche pour le Développement ( IRD ) -Aix Marseille Université ( AMU ) -Collège de France ( CdF ) -Institut National de la Recherche Agronomique ( INRA ) -Institut national des sciences de l'Univers ( INSU - CNRS ), Centre de Recherches et d'Applications Pédagogiques en Langues ( CRAPEL ), Space Sciences Laboratory [Berkeley] ( SSL ), Université de Mons ( UMons ), Planning and Transport Research Centre ( PATREC ) -Planning and Transport Research Centre ( PATREC ), University College Cork ( UCC ), Université Paris-Sud - Paris 11 ( UP11 ) -Commissariat à l'énergie atomique et aux énergies alternatives ( CEA ) -Université Paris-Saclay-Centre National de la Recherche Scientifique ( CNRS ), Ecole Nationale Supérieure de Chimie de Paris- Chimie ParisTech-PSL ( ENSCP ) -Centre National de la Recherche Scientifique ( CNRS ), Wageningen University and Research Centre [Wageningen] ( WUR ), ESPCI ParisTech, Technische Universität Berlin ( TUB ), Lipides - Nutrition - Cancer (U866) ( LNC ), Université de Bourgogne ( UB ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Ecole Nationale Supérieure de Biologie Appliquée à la Nutrition et à l'Alimentation de Dijon ( ENSBANA ), Centre de recherche Paul Pascal, CNRS, Université de Bordeaux ( UPR8641 ), Centre de Recherche Paul Pascal, CNRS, Université de Bordeaux, University Durham, University of California [Davis] ( UC Davis ), Université Paris-Sud - Paris 11 (UP11)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)-Université Paris-Sud - Paris 11 (UP11)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)-Institut de Biologie Intégrative de la Cellule (I2BC), Université Paris-Sud - Paris 11 (UP11)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)-Université Paris-Sud - Paris 11 (UP11)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS), Université Paris-Sud - Paris 11 (UP11)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS), [GIN] Grenoble Institut des Neurosciences (GIN), Helmholtz Institute for Pharmaceutical Research Saarland (HIPS), and Saarland University, Building A4.1, 66123 Saarbruecken, Germany.
Subjects: MESH : Protein Biosynthesis, protein synthesis, Operon, MESH : Polysaccharides, International Cooperation, MESH: Plants, plant, Review, MESH: Terpenes, gene cluster, polyketide, data base, genetic database, Gene cluster, acyltransferase, Databases, Genetic, MESH : Metagenome, MESH : Genetic Markers, genetics, terpene, GeneralLiterature_REFERENCE(e.g.,dictionaries,encyclopedias,glossaries), ComputingMilieux_MISCELLANEOUS, MESH : Peptides, MESH: Peptides, biology, fungus, nonribosomal peptide synthesis, Plants, bacterium, peptide, priority journal, MESH: Protein Biosynthesis, Multigene Family, MESH : Terpenes, MESH: Computational Biology, Genetic Markers, MESH: Terminology as Topic, Bioinformatics, MESH : Multigene Family, biological activity, Article, metagenome, Alkaloids, Manchester Institute of Biotechnology, Terminology as Topic, Bioinformatica, MESH : Bacteria, Peptide Biosynthesis, MESH : Databases, Genetic, Molecular Biology, MESH : Fungi, MESH: Polyketides, standardization, secondary metabolism, [ SDV ] Life Sciences [q-bio], Bacteria, ta1182, Computational Biology, MESH : Terminology as Topic, operon, Laboratorium voor Phytopathologie, MESH: International Cooperation, gene function, Metagenomics, polysaccharide, Laboratory of Phytopathology, chemical structure, Metagenome, MESH: Multigene Family, EPS, biosynthesis, Peptides, MESH : Computational Biology, MESH : International Cooperation, [SDV]Life Sciences [q-bio], MESH: Genetic Markers, information, MESH : Alkaloids, Synthetic biology, MESH: Peptide Biosynthesis, Nucleic Acid-Independent, database, MESH: Databases, Genetic, Genetics, MESH : Polyketides, MESH : Peptide Biosynthesis, Nucleic Acid-Independent, ddc:540, standards, Peptide Biosynthesis, Nucleic Acid-Independent, ComputingMethodologies_DOCUMENTANDTEXTPROCESSING, nomenclature, genetic marker, alkaloid derivative, MESH: Fungi, Biology, MESH : Plants, peptide derivative, Polyketide, MESH: Alkaloids, Polysaccharides, ddc:570, Life Science, 14. Life underwater, Secondary metabolism, enzyme specificity, Gene, nonhuman, Terpenes, Fungi, nucleotide sequence, Cell Biology, MESH: Metagenome, ResearchInstitutes_Networks_Beacons/manchester_institute_of_biotechnology, alkaloid, MESH: Bacteria, MESH: Polysaccharides, 13. Climate action, Polyketides, Protein Biosynthesis, synthetic biology, metabolism
Abstract: M.H.M. was supported by a Rubicon fellowship of the Netherlands Organization for Scientific Research (NWO;Rubicon 825.13.001). The work of R.K. was supported by the European Union’s Seventh Framework Programme(Joint Call OCEAN.2011–2: Marine microbial diversity—new insights into marine ecosystems functioning and its biotechnological potential) under the grant agreement no.287589 (Micro B3). M.C. was supported by a Biotechnology and Biological Sciences Research Council (BBSRC)studentship (BB/J014478/1). The GSC is supported by funding from the Natural Environment Research Council(UK), the National Institute for Energy Ethics and Society(NIEeS; UK), the Gordon and Betty Moore Foundation,the National Science Foundation (NSF; US) and the US Department of Energy. The Manchester Synthetic Biology Research Centre, SYNBIOCHEM, is supported by BBSRC/Engineering and Physical Sciences Research Council(EPSRC) grant BB/M017702/1, Medema, M.H., Kottmann, R., Yilmaz, P., Cummings, M., Biggins, J.B., Blin, K., De Bruijn, I., Chooi, Y.H., Claesen, J., Coates, R.C., Cruz-Morales, P., Duddela, S., Düsterhus, S., Edwards, D.J., Fewer, D.P., Garg, N., Geiger, C., Gomez-Escribano, J.P., Greule, A., Hadjithomas, M., Haines, A.S., Helfrich, E.J.N., Hillwig, M.L., Ishida, K., Jones, A.C., Jones, C.S., Jungmann, K., Kegler, C., Kim, H.U., Kötter, P., Krug, D., Masschelein, J., Melnik, A.V., Mantovani, S.M., Monroe, E.A., Moore, M., Moss, N., Nützmann, H.-W., Pan, G., Pati, A., Petras, D., Reen, F.J., Rosconi, F., Rui, Z., Tian, Z., Tobias, N.J., Tsunematsu, Y., Wiemann, P., Wyckoff, E., Yan, X., Yim, G., Yu, F., Xie, Y., Aigle, B., Apel, A.K., Balibar, C.J., Balskus, E.P., Barona-Gómez, F., Bechthold, A., Bode, H.B., Borriss, R., Brady, S.F., Brakhage, A.A., Caffrey, P., Cheng, Y.Q., Clardy, J., Cox, R.J., De Mot, R., Donadio, S., Donia, M.S., Van Der Donk, W.A., Dorrestein, P.C., Doyle, S., Driessen, A.J.M., Ehling-Schulz, M., Entian, K.-D., Fischbach, M.A., Gerwick, L., Gerwick, W.H., Gross, H., Gust, B., Hertweck, C., Höfte, M., Jensen, S.E., Ju, J., Katz, L., Kaysser, L., Klassen, J.L., Keller, N.P., Kormanec, J., Kuipers, O.P., Kuzuyama, T., Kyrpides, N.C., Kwon, H.-J., Lautru, S., Lavigne, R., Lee, C.Y., Linquan, B., Liu, X., Liu, W., Luzhetskyy, A., Mahmud, T., Mast, Y., Méndez, C., Metsä-Ketelä, M., Micklefield, J., Mitchell, D.A., Moore, B.S., Moreira, L.M., Müller, R., Neilan, B.A., Nett, M., Nielsen, J., O'Gara, F., Oikawa, H., Osbourn, A., Osburne, M.S., Ostash, B., Payne, S.M., Pernodet, J.-L., Petricek, M., Piel, J., Ploux, O., Raaijmakers, J.M., Salas, J.A., Schmitt, E.K., Scott, B., Seipke, R.F., Shen, B., Sherman, D.H., Sivonen, K., Smanski, M.J., Sosio, M., Stegmann, E., Süssmuth, R.D., Tahlan, K., Thomas, C.M., Tang, Y., Truman, A.W., Viaud, M., Walton, J.D., Walsh, C.T., Weber, T., Van Wezel, G.P., Wilkinson, B., Willey, J.M., Wohlleben, W., Wright, G.D., Ziemert, N., Zhang, C., Zotchev, S.B., Breitling, R., Takano, E., Glöckner, F.O.
Published: 2015

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