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)

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    67 Citations (Scopus)

    Abstract

    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
    Volume58
    Issue number11
    Early online date25 Aug 2014
    DOIs
    Publication statusPublished - Nov 2014

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  • Research Output

    • 67 Citations
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    Correction for Arora et al., "Respiratory Flexibility in Response to Inhibition of Cytochrome c Oxidase in Mycobacterium tuberculosis"

    Arora, K., Ochoa-Montaño, B., Tsang, P. S., Blundell, T. L., Dawes, S. S., Mizrahi, V., Bayliss, T., Mackenzie, C. J., Cleghorn, L. A. T., Ray, P. C., Wyatt, P. G., Uh, E., Lee, J., Barry, C. E. & Boshoff, H. I., Sep 2017, In : Antimicrobial Agents and Chemotherapy. 61, 9, 1 p., e01429-17 .

    Research output: Contribution to journalArticle

    Cite this

    Arora, K., Ochoa-Montaño, B., Tsang, P. S., Blundell, T. L., Dawes, S. S., Mizrahi, V., Bayliss, T., Mackenzie, C. J., Cleghorn, L. A. T., Ray, P. C., Wyatt, P. G., Uh, E., Lee, J., Barry, C. E., & Boshoff, H. I. (2014). Respiratory flexibility in response to inhibition of cytochrome c oxidase in Mycobacterium tuberculosis. Antimicrobial Agents and Chemotherapy, 58(11), 6962-6965. https://doi.org/10.1128/AAC.03486-14