Bedaquiline targets the ε subunit of mycobacterial F-ATP synthase

Subhashri Kundu, Goran Biukovic, Gerhard Grüber, Thomas Dick

Research output: Contribution to journalArticle

27 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 languageEnglish (US)
Pages (from-to)6977-6979
Number of pages3
JournalAntimicrobial agents and chemotherapy
Volume60
Issue number11
DOIs
StatePublished - Nov 1 2016

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All Science Journal Classification (ASJC) codes

  • Pharmacology
  • Pharmacology (medical)
  • Infectious Diseases

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