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

doi:10.1128/AAC.03486-14

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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110 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 bc₁complex and highlight the risk of targeting energy metabolism with new drugs.

Original language	English
Pages (from-to)	6962-6965
Number of pages	4
Journal	Antimicrobial Agents and Chemotherapy
Volume	58
Issue number	11
Early online date	25 Aug 2014
DOIs	https://doi.org/10.1128/AAC.03486-14
Publication status	Published - Nov 2014

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10.1128/AAC.03486-14

110 Citations
1 Article

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., Sept 2017, In: Antimicrobial Agents and Chemotherapy. 61, 9, 1 p., e01429-17 .
Research output: Contribution to journal › Article

Open Access

History and science come together at new Dundee TB exhibition
Floyd, A., Cleghorn, L., Tamaki, F., Davis, S., Hedges, L. & Mackintosh, A.
6/10/23
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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

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title = "Respiratory flexibility in response to inhibition of cytochrome c oxidase in Mycobacterium tuberculosis",

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.",

author = "Kriti Arora and Bernardo Ochoa-Monta{\~n}o and Tsang, {Patricia S.} and Blundell, {Tom L.} and Dawes, {Stephanie S.} and Valerie Mizrahi and Tracy Bayliss and Mackenzie, {Claire J.} and Cleghorn, {Laura A. T.} and Ray, {Peter C.} and Wyatt, {Paul G.} and Eugene Uh and Jinwoo Lee and Barry, {Clifton E.} and Boshoff, {Helena I.}",

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Arora, K, Ochoa-Montaño, B, Tsang, PS, Blundell, TL, Dawes, SS, Mizrahi, V, Bayliss, T , Mackenzie, CJ , Cleghorn, LAT, Ray, PC, Wyatt, PG, Uh, E, Lee, J, Barry, CE & Boshoff, HI 2014, 'Respiratory flexibility in response to inhibition of cytochrome c oxidase in Mycobacterium tuberculosis', Antimicrobial Agents and Chemotherapy, vol. 58, no. 11, pp. 6962-6965. https://doi.org/10.1128/AAC.03486-14

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AU - Blundell, Tom L.

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AU - Mizrahi, Valerie

AU - Bayliss, Tracy

AU - Mackenzie, Claire J.

AU - Cleghorn, Laura A. T.

AU - Ray, Peter C.

AU - Wyatt, Paul G.

AU - Uh, Eugene

AU - Lee, Jinwoo

AU - Barry, Clifton E.

AU - Boshoff, Helena I.

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AB - 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.

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DO - 10.1128/AAC.03486-14

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SN - 0066-4804

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EP - 6965

JO - Antimicrobial Agents and Chemotherapy

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ER -

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

Abstract

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

History and science come together at new Dundee TB exhibition

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

Abstract

UN SDGs

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

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History and science come together at new Dundee TB exhibition

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