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Article Dans Une Revue PLoS Pathogens Année : 2021

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

Résumé

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 Δ rv0180c :: 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 Δ rv0180c :: 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.
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Dates et versions

hal-03420756 , version 1 (17-10-2022)

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Delphine Payros, Henar Alonso, Wladimir Malaga, Arnaud Volle, Serge Mazères, et al.. Rv0180c contributes to Mycobacterium tuberculosis cell shape and to infectivity in mice and macrophages. PLoS Pathogens, 2021, 17 (11), pp.e1010020. ⟨10.1371/journal.ppat.1010020⟩. ⟨hal-03420756⟩
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