Rv0180c contributes to M. tuberculosis cell shape and to infectivity in mice and host cells

ABSTRACT: 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 lung 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 lung. We found several genes encoding known virulence factors and 3 new candidates not previously described: rv0180c, rv1179c and rv1592c. We focused on the gene, rv0180c, of unknown function and demonstrated its requirement for seeding in the lung of mice and for initiating the infection. We found that Rv0180c enhances entry into macrophages and epithelial cells. In human macrophages, this effect is mediated by the complement-receptor 3, CR3, a major phagocytic receptor for M. tuberculosis. Blocking the CR3 lectin site abolished the difference between the wild-type parental strain and the rv0180c::km mutant with regard to bacterial entry into macrophages. However, we did not detect any difference in the production of both CR3-known ligands (glucan, arabinomannan, mannan), CR3-modulating lipids (phthiocerol dimycocerosate) or proteins in the outermost layer of the rv0180c::km mutant in comparison to the wild-type or complemented strains. 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 may explain the lower engagement of receptors and open a new perspective on the modulation of bacterial infectivity.

INSTRUMENT(S): Orbitrap Fusion

ORGANISM(S): Mycobacterium Tuberculosis H37rv_2009

SUBMITTER: Alexandre STELLA  

LAB HEAD: Christophe Guilhot

PROVIDER: PXD024319 | Pride | 2022-02-16

REPOSITORIES: Pride