Carbon dioxide regulates <i>Mycobacterium tuberculosis</i> PhoPR signaling and virulence.

ABSTRACT: The Mycobacterium tuberculosis (Mtb) two-component regulatory system PhoPR is implicated in pH sensing within the macrophage because it is strongly induced by acidic pH both in vitro and the macrophage phagosome. The carbonic anhydrase (CA) inhibitor ethoxzolamide inhibits PhoPR signaling supporting the hypothesis that CO₂ may also play a role in regulating PhoPR. Here, we show that increasing CO₂ concentration induces PhoPR signaling, at both pH 7.0 and pH 5.7. At acidic pH 5.7, a normally strong inducer of PhoPR signaling, increasing CO₂ from 0.5% to 5% further induces the pathway, showing CO₂ acts synergistically with acidic pH to induce the PhoPR regulon. Based on these findings, we propose that PhoPR functions as a CO₂

SUBMITTER: Dechow SJ 

PROVIDER: S-EPMC11895460 | biostudies-literature | 2025 Mar

REPOSITORIES: biostudies-literature