Respiratory flexibility in response to inhibition of cytochrome c oxidase in Mycobacterium tuberculosis

Kriti Arora, Bernardo Ochoa-Montaño, Patricia S. Tsang, Tom L. Blundell, Stephanie S. Dawes, Valerie Mizrahi, Tracy Bayliss, Claire J. Mackenzie, Laura A. T. Cleghorn, Peter C. Ray, Paul G. Wyatt, Eugene Uh, Jinwoo Lee, Clifton E. Barry, Helena I. Boshoff (Lead / Corresponding author)

    Research output: Contribution to journalArticlepeer-review

    79 Citations (Scopus)


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

    Original languageEnglish
    Pages (from-to)6962-6965
    Number of pages4
    JournalAntimicrobial Agents and Chemotherapy
    Issue number11
    Early online date25 Aug 2014
    Publication statusPublished - Nov 2014

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