Integrated sensing of host stresses by inhibition of a cytoplasmic two-component system controls M. tuberculosis acute lung infection.

ABSTRACT: Bacterial pathogens that infect phagocytic cells must deploy mechanisms that sense and neutralize host microbicidal effectors. For Mycobacterium tuberculosis, the causative agent of tuberculosis, these mechanisms allow the bacterium to rapidly adapt from aerosol transmission to initial growth in the lung alveolar macrophage. Here, we identify a branched signaling circuit in M. tuberculosis that controls growth in the lung through integrated direct sensing of copper ions and nitric oxide by coupled activity of the Rip1 intramembrane protease and the PdtaS/R two-component system. This circuit uses a two-signal mechanism to inactivate the PdtaS/PdtaR two-component system, which constitutively represses virulence gene expression. Cu and NO inhibit the PdtaS sensor kinase through

SUBMITTER: Buglino JA 

PROVIDER: S-EPMC8131098 | biostudies-literature | 2021 May

REPOSITORIES: biostudies-literature