Chalkophore mediated respiratory oxidase flexibility controls <i>M. tuberculosis</i> virulence.

ABSTRACT: Oxidative phosphorylation has emerged as a critical therapeutic vulnerability of M. tuberculosis (Mtb). However, it is unknown how intracellular bacterial pathogens such as Mtb maintain respiration during infection despite the chemical effectors of host immunity. Mtb synthesizes diisonitrile lipopeptides that tightly chelate copper, but the role of these chalkophores in host-pathogen interactions is also unknown. We demonstrate that M. tuberculosis chalkophores maintain the function of the heme-copper bcc:aa ₃ respiratory supercomplex under copper limitation. Chalkophore deficiency impairs Mtb survival, respiration to oxygen, and ATP production under copper deprivation in culture, effects that are exacerbated by loss of the

SUBMITTER: Buglino JA 

PROVIDER: S-EPMC11030325 | biostudies-literature | 2025 Mar

REPOSITORIES: biostudies-literature