Respiratory Flexibility in Response to Inhibition of CytochromecOxidase in Mycobacterium tuberculosis

Abstract

ABSTRACTWe report here a series of five chemically diverse scaffolds that havein vitroactivities on replicating and hypoxic nonreplicating bacilli by targeting the respiratorybc1complex inMycobacterium tuberculosisin a strain-dependent manner. Deletion of the cytochromebdoxidase generated a hypersusceptible mutant in which resistance was acquired by a mutation inqcrB. These results highlight the promiscuity of thebc1complex and the risk of targeting energy metabolism with new drugs.