Respiratory Flexibility in Response to Inhibition of Cytochrome <i>c</i> Oxidase in Mycobacterium tuberculosis
Kriti Arora(National Institutes of Health), Bernardo Ochoa‐Montaño(University of Cambridge), Patricia Tsang(National Institutes of Health), Tom L. Blundell(University of Cambridge), Stephanie S. Dawes(University of the Witwatersrand), Valerie Mizrahi(University of Cape Town), Tracy Bayliss(University of Dundee), Claire J. Mackenzie(University of Dundee), Laura A. T. Cleghorn(University of Dundee), Peter C. Ray(University of Dundee), Paul G. Wyatt(University of Dundee), Eugene Uh(National Institutes of Health), Jinwoo Lee(National Institutes of Health), Clifton E. Barry(National Institutes of Health), Helena I. Boshoff(National Institutes of Health)
Cited by 129Open Access
Abstract
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.
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