Parallel in vivo experimental evolution reveals that increased stress resistance was key for the emergence of persistent tuberculosis bacilli

Autor: Alexandre Pawlik, Roland Brosch, Christophe Guilhot, Flavie Moreau, Philip Supply, Rudy Antoine, Ali Hassan, Catherine Astarie-Dequeker, Antonio Peixoto, Aideen C. Allen, Wladimir Malaga, Céline Berrone, Arnaud Volle, Cyril Gaudin, Wafa Frigui
Přispěvatelé: Institut de pharmacologie et de biologie structurale (IPBS), Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Centre National de la Recherche Scientifique (CNRS), Genoscreen [Lille], Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP), Centre d’Infection et d’Immunité de Lille - INSERM U 1019 - UMR 9017 - UMR 8204 (CIIL), 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), Pathogénomique mycobactérienne intégrée - Integrated Mycobacterial Pathogenomics, Université Paris Cité (UPCité)-Microbiologie Intégrative et Moléculaire (UMR6047), Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), This project received funding from the European Respiratory Society and the European Union’s H2020 research and innovation programme under the Marie Sklodowska–Curie grant agreement no. 713406 awarded to A.C.A. This work was also supported by grants from the French National Research Agency (TBemerg contract no. ANR-16-CE35-0009 awarded to R.B., P.S. and C. Guilhot, Equipex ANINFIMIP ANR-11-EQUIPEX-0003 to C. Guilhot, Labex ANR-10-LABX-62-IBEID awarded to R.B.), the European Union (PathoNgenTrace contract no. FP7-278864 awarded to P.S.), and the Fondation pour la Recherche Médicale (Equipe FRM 2016 DEQ20160334879), the Fondation Bettencourt Schueller and the Fondation MSDAvenir (Fight-TB project) to C. Guilhot., ANR-16-CE35-0009,TBemerg,Naissance d'un tueur: facteurs génétiques et adaptations métaboliques impliquées dans l'émergence des bacilles tuberculeux épidémiques(2016), ANR-11-EQPX-0003,ANINFIMIP,Equipements plateforme animalerie infectieuse de haute-sécurité de Midi Pyrénées(2011), ANR-10-LABX-0062,IBEID,Integrative Biology of Emerging Infectious Diseases(2010), European Project: 713406,H2020,H2020-MSCA-COFUND-2015,RESPIRE 3(2016), European Project: 278864,EC:FP7:HEALTH,FP7-HEALTH-2011-two-stage,PATHONGEN-TRACE(2012), Centre National de la Recherche Scientifique (CNRS)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées, 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, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS), GUILHOT, Christophe, Naissance d'un tueur: facteurs génétiques et adaptations métaboliques impliquées dans l'émergence des bacilles tuberculeux épidémiques - - TBemerg2016 - ANR-16-CE35-0009 - AAPG2016 - VALID, Equipements plateforme animalerie infectieuse de haute-sécurité de Midi Pyrénées - - ANINFIMIP2011 - ANR-11-EQPX-0003 - EQPX - VALID, Integrative Biology of Emerging Infectious Diseases - - IBEID2010 - ANR-10-LABX-0062 - LABX - VALID, REspiratory Science Promoted by International Research Exchanges 3 - RESPIRE 3 - - H20202016-09-01 - 2021-08-31 - 713406 - VALID, Next Generation Genome Based High Resolution Tracing of Pathogens - PATHONGEN-TRACE - - EC:FP7:HEALTH2012-01-01 - 2016-06-30 - 278864 - VALID
Jazyk: angličtina
Předmět:
Zdroj: Nature Microbiology
Nature Microbiology, 2021, 6 (8), pp.1082-1093. ⟨10.1038/s41564-021-00938-4⟩
Nature Microbiology, Nature Publishing Group, 2021, 6 (8), pp.1082-1093. ⟨10.1038/s41564-021-00938-4⟩
ISSN: 2058-5276
DOI: 10.1038/s41564-021-00938-4
Popis: International audience; Pathogenomic evidence suggests that Mycobacterium tuberculosis evolved from an environmental ancestor similar to Mycobacterium canettii, a rare human pathogen. However, the adaptations responsible for the transition from an environmental mycobacterium to an obligate human pathogen are poorly characterised. The ability to persist in the human host appears to be one important trait. Here we set out to identify the adaptations that contribute to the evolution of persistence in M. tuberculosis. By using experimental evolution of 8 M. canettii populations in mice, we selected mutants with enhanced persistence in vivo when compared to parental strains, which were thus phenotypically closer to M. tuberculosis. Genome sequencing of 140 M. canettii mutants and complementation analysis revealed that mutations in two loci were responsible for the enhanced persistence phenotypes. Most of the tested mutants were more resistant than their parental strains to nitric oxide, which is an important effector of immunity against M. tuberculosis infection. This resistance was common to modern M. tuberculosis strains but not to M. canettii strains. Our findings demonstrate phenotypic convergence during the experimental evolution of M. canettii, which mirrors natural evolution of M. tuberculosis. Furthermore, they indicate that the ability to withstand hostinduced stresses, such as nitric oxide, was key for the emergence of persistent M. tuberculosis.
Databáze: OpenAIRE
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