Respiratory flexibility in response to inhibition of cytochrome C oxidase in Mycobacterium tuberculosis.

Antimicrobial agents and chemotherapy, Volume: 58, Issue: 11
November 25, 2014
Kriti Arora K, Bernardo Ochoa-MontaƱo B, Patricia S Tsang PS, Tom L Blundell TL, Stephanie S Dawes SS, Valerie Mizrahi V, Tracy Bayliss T, Claire J Mackenzie CJ, Laura A T Cleghorn LA, Peter C Ray PC, Paul G Wyatt PG, Eugene Uh E, Jinwoo Lee J, Clifton E Barry CE, Helena I Boshoff HI

We report here a series of five chemically diverse scaffolds that have in vitro activities on replicating and hypoxic nonreplicating bacilli by targeting the respiratory bc1 complex in Mycobacterium tuberculosis in a strain-dependent manner. Deletion of the cytochrome bd oxidase generated a hypersusceptible mutant in which resistance was acquired by a mutation in qcrB. These results highlight the promiscuity of the bc1 complex and the risk of targeting energy metabolism with new drugs.

Courtesy of the U.S. National Library of Medicine