Bedaquiline targets the ε subunit of mycobacterial F-ATP synthase

Subhashri Kundu; Goran Biukovic; Gerhard Grüber; Thomas Dick

doi:10.1128/AAC.01291-16

Bedaquiline targets the ε subunit of mycobacterial F-ATP synthase

Subhashri Kundu
, Goran Biukovic
, Gerhard Grüber
, Thomas Dick

Center for Discovery and Innovation

National University of Singapore
Nanyang Technological University

Research output: Contribution to journal › Article › peer-review

69 Scopus citations

Abstract

The tuberculosis drug bedaquiline inhibits mycobacterial F-ATP synthase by binding to its c subunit. Using the purified ε subunit of the synthase and spectroscopy, we previously demonstrated that the drug interacts with this protein near its unique tryptophan residue. Here, we show that replacement of ε's tryptophan with alanine resulted in bedaquiline hypersusceptibility of the bacteria. Overexpression of the wild-type ε subunit caused resistance. These results suggest that the drug also targets the ε subunit.

Original language	English
Pages (from-to)	6977-6979
Number of pages	3
Journal	Antimicrobial Agents and Chemotherapy
Volume	60
Issue number	11
DOIs	https://doi.org/10.1128/AAC.01291-16
State	Published - 1 Nov 2016

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SDG 3 Good Health and Well-being

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10.1128/AAC.01291-16

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abstract = "The tuberculosis drug bedaquiline inhibits mycobacterial F-ATP synthase by binding to its c subunit. Using the purified ε subunit of the synthase and spectroscopy, we previously demonstrated that the drug interacts with this protein near its unique tryptophan residue. Here, we show that replacement of ε's tryptophan with alanine resulted in bedaquiline hypersusceptibility of the bacteria. Overexpression of the wild-type ε subunit caused resistance. These results suggest that the drug also targets the ε subunit.",

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AB - The tuberculosis drug bedaquiline inhibits mycobacterial F-ATP synthase by binding to its c subunit. Using the purified ε subunit of the synthase and spectroscopy, we previously demonstrated that the drug interacts with this protein near its unique tryptophan residue. Here, we show that replacement of ε's tryptophan with alanine resulted in bedaquiline hypersusceptibility of the bacteria. Overexpression of the wild-type ε subunit caused resistance. These results suggest that the drug also targets the ε subunit.

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Bedaquiline targets the ε subunit of mycobacterial F-ATP synthase

Abstract

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