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1. Gut Dysbiosis during Influenza Contributes to Pulmonary Pneumococcal Superinfection through Altered Short-Chain Fatty Acid Production

Author

Valentin Sencio, Adeline Barthelemy, Luciana P. Tavares, Marina G. Machado, Daphnée Soulard, Céline Cuinat, Celso Martins Queiroz-Junior, Marie-Louise Noordine, Sophie Salomé-Desnoulez, Lucie Deryuter, Benoit Foligné, Céline Wahl, Benoit Frisch, Angelica T. Vieira, Christophe Paget, Graeme Milligan, Trond Ulven, Isabelle Wolowczuk, Christelle Faveeuw, Ronan Le Goffic, Muriel Thomas, Stéphanie Ferreira, Mauro M. Teixeira, and François Trottein

Subjects
Biology (General), QH301-705.5
Abstract

Summary: Secondary bacterial infections often complicate viral respiratory infections. We hypothesize that perturbation of the gut microbiota during influenza A virus (IAV) infection might favor respiratory bacterial superinfection. Sublethal infection with influenza transiently alters the composition and fermentative activity of the gut microbiota in mice. These changes are attributed in part to reduced food consumption. Fecal transfer experiments demonstrate that the IAV-conditioned microbiota compromises lung defenses against pneumococcal infection. In mechanistic terms, reduced production of the predominant short-chain fatty acid (SCFA) acetate affects the bactericidal activity of alveolar macrophages. Following treatment with acetate, mice colonized with the IAV-conditioned microbiota display reduced bacterial loads. In the context of influenza infection, acetate supplementation reduces, in a free fatty acid receptor 2 (FFAR2)-dependent manner, local and systemic bacterial loads. This translates into reduced lung pathology and improved survival rates of double-infected mice. Lastly, pharmacological activation of the SCFA receptor FFAR2 during influenza reduces bacterial superinfection. : Sencio et al. provide insights into the mechanisms that underlie bacterial superinfection post-influenza. The authors demonstrate that influenza infection remotely alters the production of short-chain fatty acids (SCFAs) by the gut microbiota. Supplementation with acetate or pharmacological activation of the SCFA receptor FFAR2 reduces susceptibility to secondary bacterial infection. Keywords: influenza A virus, bacterial superinfection, gut microbiota, microbial dysbiosis, food restriction, short-chain fatty acid, acetate, free fatty acid receptor 2, macrophages

Published
2020
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2. Evolutionary history and global spread of the Mycobacterium tuberculosis Beijing lineage

Author

Sabine Rüsch-Gerdes, Hans P eter Beck, Vladyslav Nikolayevskyy, Irina Kontsevaya, Petras Stakenas, Kadri Toit, Shinji Maeda, Eman Aleksic, Marie Ballif, Stefano Mona, Troels Lillebaek, Maryline Bonnet, Caroline Allix-Béguec, Sophie Lecher, Robin M. Warren, Isdore Chola Shamputa, Francesca Barletta, Isolina Campos-Herrero, Wei wei Jiao, Thomas Kohl, Suzanne M. Crowe, Ewa Augustynowicz-Kopeć, Solomon Ghebremichael, Branislava Savic, Francis Varaine, Dragana Vuković, Camille Blin, Annick Antierens, Li Hwei Sng, Maryse Fauville-Dufaux, Céline Wahl, Thierry Wirth, Stefan Niemann, Eve Willery, Helen Cox, Valeriu Crudu, Emanuele Borroni, Sebastien Gagneux, Philip Supply, Sven Hoffner, Adong Shen, Stobdan Kalon, Michael Rasmussen, Francis Drobniewski, Igor Mokrousov, Michael G. B. Blum, Madeleine Hanekom, Sofía Samper, Matthias Merker, Clifton E. Barry, Nicolas Duforet-Frebourg, Roland Diel, Nalin Rastogi, Daniela Maria Cirillo, Elisabeth Sanchez-Padilla, Molecular Mycobacteriology, Research Center Borstel - Leibniz Lung Center [Germany], Institut de Systématique, Evolution, Biodiversité (ISYEB ), Muséum national d'Histoire naturelle (MNHN)-Université Pierre et Marie Curie - Paris 6 (UPMC)-École Pratique des Hautes Études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Centre National de la Recherche Scientifique (CNRS), Laboratoire Biologie Intégrative des Population, Evolution Moléculaire, École Pratique des Hautes Études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL), Biologie Computationnelle et Mathématique (TIMC-IMAG-BCM), Techniques de l'Ingénierie Médicale et de la Complexité - Informatique, Mathématiques et Applications, Grenoble - UMR 5525 (TIMC-IMAG), Université Joseph Fourier - Grenoble 1 (UJF)-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 Joseph Fourier - Grenoble 1 (UJF)-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), Centre d’Infection et d’Immunité de Lille - INSERM U 1019 - UMR 9017 - UMR 8204 (CIIL), Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Centre National de la Recherche Scientifique (CNRS), National Reference Center for Mycobacteria, Institut Pasteur de Saint-Pétersbourg, Réseau International des Instituts Pasteur (RIIP), Centre for Biomedical Research, Burnet Institute [Melbourne, Victoria], genoscreen, GenoScreen, Medical Department, Médecins sans Frontières [Genève] (MSF), Department of Microbiology, National Tuberculosis and Lung Diseases Research Institute, Institute of Social and Preventive Medicine, Universität Bern [Bern] (UNIBE), Instituto de Medicina Tropical Alexander von Humboldt, Molecular Epidemiology Unit–Tuberculosis, Instituto de Medicina Tropical 'Alexander von Humboldt' (IMT AvH), Universidad Peruana Cayetano Heredia (UPCH)-Universidad Peruana Cayetano Heredia (UPCH), Medical Parasitology and Infection Biology [Basel, Suisse] (MPI), Swiss Tropical and Public Health Institute [Basel], Laboratoire de Recherche en Informatique d'Amiens (LaRIA), Université de Picardie Jules Verne (UPJV)-Centre National de la Recherche Scientifique (CNRS), Epicentre [Paris] [Médecins Sans Frontières], Emerging Bacterial Pathogen Unit, San Raffaele Scientific Institute, hospital Universitario de Gran Canaria Dr Negrin, Macfarlane Burnet Institute for Medical Research, Laboratoire Jean Alexandre Dieudonné (LJAD), Université Nice Sophia Antipolis (1965 - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Centre National de la Recherche Scientifique (CNRS)-Université Côte d'Azur (UCA), PHE National Mycobacterial Reference Laboratory and Clinical TB and HIV Group, Queen Mary's School of Medicine and Dentistry, Division of Infectious Diseases, Imperial College London, Centre national de Référence et Laboratoire Tuberculose et Mycobactéries = National Reference Centre of Tuberculosis and Mycobacteria [Brussels] (CNR), Institut Scientifique de Santé Publique [Belgique] - Scientific Institute of Public Health [Belgium] (WIV-ISP), Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP), MRC National Institute for Medical Research, Department of Preparedness, Swedish Institute for Infectious Disease Control, Faculty of Medicine and Health Sciences, stellen, Key Laboratory of Major Diseases in Children, Beijing Children's Hospital affiliated to Capital Medical University-Beijing Pediatric Research Institute-Chine - Ministry of Education, Samara Oblast TB Service, Research institute of Tuberculosis, Anti-tuberculosis Association, Institut Pasteur de la Guadeloupe, LAboratoire de Recherche en Mécanique Appliquée (LARMAUR), Université de Rennes (UR)-Centre National de la Recherche Scientifique (CNRS), Mycobacteriology Unit, Prince Leopold Institute of Tropical Medicine, Microbiology Unit, Tropical Diseases Research Centre [Zambia] (TDRC), Alcatel-Thalès III-V lab (III-V Lab), THALES [France]-ALCATEL, Central Tuberculosis Laboratory, Singapore General Hospital, Medecins Sans Frontieres (Medecins Sans Frontieres), Médecins Sans Frontières, DTU Fotonik - Department of Photonics Engineering, Danmarks Tekniske Universitet = Technical University of Denmark (DTU), molecular biology and human genetics, Stell, Molecular Mycobacteriology Group, National Reference Center for Mycobacyeria, Origine, structure et évolution de la biodiversité (OSEB), Muséum national d'Histoire naturelle (MNHN)-Centre National de la Recherche Scientifique (CNRS), We acknowledge J. Peh for her assistance and support in the study andI. Comas for statistical advice. Parts of this work have been supported by grantsfrom the European Community’s Seventh Framework Programme (FP7/2007-2013) under grant agreement 278864 in the framework of the European UnionPathoNGenTrace project and grant agreement 223681 in the framework of theTB-PAN-NET project. We also thank Action Transversale du Muséum Nationald’Histoire Naturelle ‘Les Microorganismes, Acteurs Clés dans les Ecosystèmes’for financial support, European Project: 223681,EC:FP7:HEALTH,FP7-HEALTH-2007-B,TB PAN-NET(2009), European Project: 278864,FP7/2007- 2013, Muséum national d'Histoire naturelle (MNHN)-École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS), École pratique des hautes études (EPHE), VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-Centre National de la Recherche Scientifique (CNRS)-Université Joseph Fourier - Grenoble 1 (UJF)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-Centre National de la Recherche Scientifique (CNRS)-Université Joseph Fourier - Grenoble 1 (UJF), Centre National de la Recherche Scientifique (CNRS)-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Université de Lille-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Pasteur de Lille, Universität Bern [Bern], Laboratoire Jean Alexandre Dieudonné (JAD), Université Côte d'Azur (UCA)-Université Nice Sophia Antipolis (... - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Centre National de la Recherche Scientifique (CNRS), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Centre National de la Recherche Scientifique (CNRS), THALES-ALCATEL, and Technical University of Denmark [Lyngby] (DTU)

Subjects
Tuberculosis, Lineage (genetic), MESH: Mutation, MESH: Mycobacterium tuberculosis, Genotype, MESH: Biological Evolution, MESH: Global Health, Biology, MESH: Genome, Bacterial, Global Health, Genetic analysis, Mycobacterium tuberculosis, MESH: Genotype, Evolution, Molecular, Phylogenetics, Tuberculosis, Multidrug-Resistant, Genetics, Global health, medicine, Humans, MESH: Phylogeny, MESH: Evolution, Molecular, MESH: Tuberculosis, Multidrug-Resistant, Phylogeny, MESH: Humans, Ecology, Population size, medicine.disease, biology.organism_classification, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, Biological Evolution, 3. Good health, Mycobacterium tuberculosis/classification/genetics/isolation & purification, Evolutionary biology, Mutation, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, Tuberculosis, Multidrug-Resistant/epidemiology/microbiology, Genome, Bacterial, purl.org/pe-repo/ocde/ford#1.06.07 [https]
Abstract

International audience; Mycobacterium tuberculosis strains of the Beijing lineage are globally distributed and are associated with the massive spread of multidrug-resistant (MDR) tuberculosis in Eurasia. Here we reconstructed the biogeographical structure and evolutionary history of this lineage by genetic analysis of 4,987 isolates from 99 countries and whole-genome sequencing of 110 representative isolates. We show that this lineage initially originated in the Far East, from where it radiated worldwide in several waves. We detected successive increases in population size for this pathogen over the last 200 years, practically coinciding with the Industrial Revolution, the First World War and HIV epidemics. Two MDR clones of this lineage started to spread throughout central Asia and Russia concomitantly with the collapse of the public health system in the former Soviet Union. Mutations identified in genes putatively under positive selection and associated with virulence might have favored the expansion of the most successful branches of the lineage.

Published
2015
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3. Proposal of a consensus set of hypervariable mycobacterial interspersed repetitive-unit-variable-number tandem-repeat loci for subtyping of mycobacterium tuberculosis Beijing isolates

Author

Igor Mokrousov, Philip Supply, Robin M. Warren, Isolina Campos-Herrero, Madeleine Hanekom, Vladyslav Nikolayevskyy, Sofía Samper, Francis Drobniewski, Irina Kontsevaya, Caroline Allix-Béguec, Shinji Maeda, Li-Hwei Sng, Nalin Rastogi, Stefan Niemann, Céline Wahl, genoscreen, GenoScreen, Faculty of Medicine and Health Sciences, stellen, PHE National Mycobacterial Reference Laboratory and Clinical TB and HIV Group, Queen Mary's School of Medicine and Dentistry, Division of Infectious Diseases, Imperial College London, Research institute of Tuberculosis, Anti-tuberculosis Association, hospital Universitario de Gran Canaria Dr Negrin, Institut Pasteur de Saint-Pétersbourg, Réseau International des Instituts Pasteur (RIIP), Molecular Mycobacteriology Group, National Reference Center for Mycobacyeria, Samara Oblast TB Service, Institut Pasteur de la Guadeloupe, LLS Aragon, Hospital Universitario Miguel Servet, Central Tuberculosis Laboratory, Singapore General Hospital, Stellenbosch University, Centre d’Infection et d’Immunité de Lille - INSERM U 1019 - UMR 9017 - UMR 8204 (CIIL), Centre National de la Recherche Scientifique (CNRS)-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Université de Lille-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP), Institut Pasteur de Lille, and Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Centre National de la Recherche Scientifique (CNRS)

Subjects
Microbiology (medical), Genetics, Molecular Epidemiology, Molecular epidemiology, Minisatellite Repeat, Strain (biology), Mycobacteriology and Aerobic Actinomycetes, Minisatellite Repeats, Mycobacterium tuberculosis, Biology, biology.organism_classification, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, Subtyping, 3. Good health, Molecular Typing, Variable number tandem repeat, Beijing, Humans, Tuberculosis, Typing
Abstract

Mycobacterium tuberculosis Beijing strains represent targets of special importance for molecular surveillance of tuberculosis (TB), especially because they are associated with spread of multidrug resistance in some world regions. Standard 24-locus mycobacterial interspersed repetitive-unit–variable-number tandem-repeat (MIRU-VNTR) typing lacks resolution power for accurately discriminating closely related clones that often compose Beijing strain populations. Therefore, we evaluated a set of 7 additional, hypervariable MIRU-VNTR loci for better resolution and tracing of such strains, using a collection of 535 Beijing isolates from six world regions where these strains are known to be prevalent. The typeability and interlaboratory reproducibility of these hypervariable loci were lower than those of the 24 standard loci. Three loci (2163a, 3155, and 3336) were excluded because of their redundant variability and/or more frequent noninterpretable results compared to the 4 other markers. The use of the remaining 4-locus set (1982, 3232, 3820, and 4120) increased the number of types by 52% (from 223 to 340) and reduced the clustering rate from 58.3 to 36.6%, when combined with the use of the standard 24-locus set. Known major clonal complexes/24-locus-based clusters were all subdivided, although the degree of subdivision varied depending on the complex. Only five single-locus variations were detected among the hypervariable loci of an additional panel of 92 isolates, representing 15 years of clonal spread of a single Beijing strain in a geographically restricted setting. On this calibrated basis, we propose this 4-locus set as a consensus for subtyping Beijing clonal complexes and clusters, after standard typing.

Published
2017
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4. SARS-CoV-2 infection in nonhuman primates alters the composition and functional activity of the gut microbiota

Author

Harry Sokol, Vanessa Contreras, Pauline Maisonnasse, Aurore Desmons, Benoit Delache, Valentin Sencio, Arnaud Machelart, Angela Brisebarre, Lydie Humbert, Lucie Deryuter, Emilie Gauliard, Severine Heumel, Dominique Rainteau, Nathalie Dereuddre-Bosquet, Elisabeth Menu, Raphael Ho Tsong Fang, Antonin Lamaziere, Loic Brot, Celine Wahl, Cyriane Oeuvray, Nathalie Rolhion, Sylvie Van Der Werf, Stéphanie Ferreira, Roger Le Grand, and François Trottein

Subjects
gut microbiota, sars-cov-2, nonhuman primates, gut dysbiosis, metabolic output, Diseases of the digestive system. Gastroenterology, RC799-869
Abstract

The current pandemic of coronavirus disease (COVID) 2019 constitutes a global public health issue. Regarding the emerging importance of the gut-lung axis in viral respiratory infections, analysis of the gut microbiota’s composition and functional activity during a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection might be instrumental in understanding and controling COVID 19. We used a nonhuman primate model (the macaque), that recapitulates mild COVID-19 symptoms, to analyze the effects of a SARS-CoV-2 infection on dynamic changes of the gut microbiota. 16S rRNA gene profiling and analysis of β diversity indicated significant changes in the composition of the gut microbiota with a peak at 10–13 days post-infection (dpi). Analysis of bacterial abundance correlation networks confirmed disruption of the bacterial community at 10–13 dpi. Some alterations in microbiota persisted after the resolution of the infection until day 26. Some changes in the relative bacterial taxon abundance associated with infectious parameters. Interestingly, the relative abundance of Acinetobacter (Proteobacteria) and some genera of the Ruminococcaceae family (Firmicutes) was positively correlated with the presence of SARS-CoV-2 in the upper respiratory tract. Targeted quantitative metabolomics indicated a drop in short-chain fatty acids (SCFAs) and changes in several bile acids and tryptophan metabolites in infected animals. The relative abundance of several taxa known to be SCFA producers (mostly from the Ruminococcaceae family) was negatively correlated with systemic inflammatory markers while the opposite correlation was seen with several members of the genus Streptococcus. Collectively, SARS-CoV-2 infection in a nonhuman primate is associated with changes in the gut microbiota’s composition and functional activity.

Published
2021
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