Rv0180c contributes to Mycobacterium tuberculosis cell shape and to infectivity in mice and macrophages

Mycobacterium tuberculosis, the main causative agent of human tuberculosis, is transmitted from person to person via small droplets containing very few bacteria. Optimizing the chance to seed in the lungs is therefore a major adaptation to favor survival and dissemination in the human population. He...

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Autores principales:	Delphine Payros, Henar Alonso, Wladimir Malaga, Arnaud Volle, Serge Mazères, Sébastien Déjean, Sophie Valière, Flavie Moreau, Stéphanie Balor, Alexandre Stella, Lucie Combes-Soia, Odile Burlet-Schiltz, Olivier Bouchez, Jérôme Nigou, Catherine Astarie-Dequeker, Christophe Guilhot
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2021
Materias:	Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/824296c90d3c48e5a2e7e7451466ccfe
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spelling	oai:doaj.org-article:824296c90d3c48e5a2e7e7451466ccfe2021-11-18T06:01:34ZRv0180c contributes to Mycobacterium tuberculosis cell shape and to infectivity in mice and macrophages1553-73661553-7374https://doaj.org/article/824296c90d3c48e5a2e7e7451466ccfe2021-11-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC8584747/?tool=EBIhttps://doaj.org/toc/1553-7366https://doaj.org/toc/1553-7374Mycobacterium tuberculosis, the main causative agent of human tuberculosis, is transmitted from person to person via small droplets containing very few bacteria. Optimizing the chance to seed in the lungs is therefore a major adaptation to favor survival and dissemination in the human population. Here we used TnSeq to identify genes important for the early events leading to bacterial seeding in the lungs. Beside several genes encoding known virulence factors, we found three new candidates not previously described: rv0180c, rv1779c and rv1592c. We focused on the gene, rv0180c, of unknown function. First, we found that deletion of rv0180c in M. tuberculosis substantially reduced the initiation of infection in the lungs of mice. Next, we established that Rv0180c enhances entry into macrophages through the use of complement-receptor 3 (CR3), a major phagocytic receptor for M. tuberculosis. Silencing CR3 or blocking the CR3 lectin site abolished the difference in entry between the wild-type parental strain and the Δrv0180c::km mutant. However, we detected no difference in the production of both CR3-known carbohydrate ligands (glucan, arabinomannan, mannan), CR3-modulating lipids (phthiocerol dimycocerosate), or proteins in the capsule of the Δrv0180c::km mutant in comparison to the wild-type or complemented strains. By contrast, we established that Rv0180c contributes to the functionality of the bacterial cell envelope regarding resistance to toxic molecule attack and cell shape. This alteration of bacterial shape could impair the engagement of membrane receptors that M. tuberculosis uses to invade host cells, and open a new perspective on the modulation of bacterial infectivity. Author summary The epidemic efficiency of tuberculosis bacilli is determined by their capacity to transmit via aerosol. Currently, the bacterial functions that favor Mycobacterium tuberculosis seeding in the lung of naïve host remain mostly unknown. Here we implemented a genome-wide approach to identify M. tuberculosis mutants deficient for seeding and early replication in the lung of mice. In addition to genes known to encode virulence factors, we identified three genes not previously described. We used complementary approaches to characterize the phenotype of a M. tuberculosis mutant with insertion within the rv0180c gene. We found that this mutant is impaired for seeding in the lung of mice and for invasion and replication in human macrophages. In macrophages, the defect relies on a lack of engagement of CR3 receptor. Although we did not detect any difference between the wild type strain and the rv0180c mutant with regard to potential CR3-ligand, we found that the bacterial cell envelope is altered in the rv0180c mutant. Our study provides new insight into bacterial genes required for early interaction of M. tuberculosis with the host and perspective to understand the bacterial functions enhancing infectivity.Delphine PayrosHenar AlonsoWladimir MalagaArnaud VolleSerge MazèresSébastien DéjeanSophie ValièreFlavie MoreauStéphanie BalorAlexandre StellaLucie Combes-SoiaOdile Burlet-SchiltzOlivier BouchezJérôme NigouCatherine Astarie-DequekerChristophe GuilhotPublic Library of Science (PLoS)articleImmunologic diseases. AllergyRC581-607Biology (General)QH301-705.5ENPLoS Pathogens, Vol 17, Iss 11 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5
spellingShingle	Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5 Delphine Payros Henar Alonso Wladimir Malaga Arnaud Volle Serge Mazères Sébastien Déjean Sophie Valière Flavie Moreau Stéphanie Balor Alexandre Stella Lucie Combes-Soia Odile Burlet-Schiltz Olivier Bouchez Jérôme Nigou Catherine Astarie-Dequeker Christophe Guilhot Rv0180c contributes to Mycobacterium tuberculosis cell shape and to infectivity in mice and macrophages
description	Mycobacterium tuberculosis, the main causative agent of human tuberculosis, is transmitted from person to person via small droplets containing very few bacteria. Optimizing the chance to seed in the lungs is therefore a major adaptation to favor survival and dissemination in the human population. Here we used TnSeq to identify genes important for the early events leading to bacterial seeding in the lungs. Beside several genes encoding known virulence factors, we found three new candidates not previously described: rv0180c, rv1779c and rv1592c. We focused on the gene, rv0180c, of unknown function. First, we found that deletion of rv0180c in M. tuberculosis substantially reduced the initiation of infection in the lungs of mice. Next, we established that Rv0180c enhances entry into macrophages through the use of complement-receptor 3 (CR3), a major phagocytic receptor for M. tuberculosis. Silencing CR3 or blocking the CR3 lectin site abolished the difference in entry between the wild-type parental strain and the Δrv0180c::km mutant. However, we detected no difference in the production of both CR3-known carbohydrate ligands (glucan, arabinomannan, mannan), CR3-modulating lipids (phthiocerol dimycocerosate), or proteins in the capsule of the Δrv0180c::km mutant in comparison to the wild-type or complemented strains. By contrast, we established that Rv0180c contributes to the functionality of the bacterial cell envelope regarding resistance to toxic molecule attack and cell shape. This alteration of bacterial shape could impair the engagement of membrane receptors that M. tuberculosis uses to invade host cells, and open a new perspective on the modulation of bacterial infectivity. Author summary The epidemic efficiency of tuberculosis bacilli is determined by their capacity to transmit via aerosol. Currently, the bacterial functions that favor Mycobacterium tuberculosis seeding in the lung of naïve host remain mostly unknown. Here we implemented a genome-wide approach to identify M. tuberculosis mutants deficient for seeding and early replication in the lung of mice. In addition to genes known to encode virulence factors, we identified three genes not previously described. We used complementary approaches to characterize the phenotype of a M. tuberculosis mutant with insertion within the rv0180c gene. We found that this mutant is impaired for seeding in the lung of mice and for invasion and replication in human macrophages. In macrophages, the defect relies on a lack of engagement of CR3 receptor. Although we did not detect any difference between the wild type strain and the rv0180c mutant with regard to potential CR3-ligand, we found that the bacterial cell envelope is altered in the rv0180c mutant. Our study provides new insight into bacterial genes required for early interaction of M. tuberculosis with the host and perspective to understand the bacterial functions enhancing infectivity.
format	article
author	Delphine Payros Henar Alonso Wladimir Malaga Arnaud Volle Serge Mazères Sébastien Déjean Sophie Valière Flavie Moreau Stéphanie Balor Alexandre Stella Lucie Combes-Soia Odile Burlet-Schiltz Olivier Bouchez Jérôme Nigou Catherine Astarie-Dequeker Christophe Guilhot
author_facet	Delphine Payros Henar Alonso Wladimir Malaga Arnaud Volle Serge Mazères Sébastien Déjean Sophie Valière Flavie Moreau Stéphanie Balor Alexandre Stella Lucie Combes-Soia Odile Burlet-Schiltz Olivier Bouchez Jérôme Nigou Catherine Astarie-Dequeker Christophe Guilhot
author_sort	Delphine Payros
title	Rv0180c contributes to Mycobacterium tuberculosis cell shape and to infectivity in mice and macrophages
title_short	Rv0180c contributes to Mycobacterium tuberculosis cell shape and to infectivity in mice and macrophages
title_full	Rv0180c contributes to Mycobacterium tuberculosis cell shape and to infectivity in mice and macrophages
title_fullStr	Rv0180c contributes to Mycobacterium tuberculosis cell shape and to infectivity in mice and macrophages
title_full_unstemmed	Rv0180c contributes to Mycobacterium tuberculosis cell shape and to infectivity in mice and macrophages
title_sort	rv0180c contributes to mycobacterium tuberculosis cell shape and to infectivity in mice and macrophages
publisher	Public Library of Science (PLoS)
publishDate	2021
url	https://doaj.org/article/824296c90d3c48e5a2e7e7451466ccfe
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Rv0180c contributes to Mycobacterium tuberculosis cell shape and to infectivity in mice and macrophages

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