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^*

^*Corresponding author for this work

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

59 Citations (Scopus)

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
Publication status	Published - Nov 1 2016
Externally published	Yes

Bibliographical note

Publisher Copyright:
Copyright © 2016 Kundu et al.

ASJC Scopus Subject Areas

Pharmacology
Pharmacology (medical)
Infectious Diseases

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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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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Bedaquiline targets the ε subunit of mycobacterial F-ATP synthase

Abstract

Bibliographical note

ASJC Scopus Subject Areas

UN SDGs

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