BEDAQUILINE TARGETS THE EPSILON SUBUNIT OF MYCOBACTERIAL F-ATP SYNTHASE

Abstract

The tuberculosis drug Bedaquiline inhibits mycobacterial F-ATP synthase by binding to its c subunit. Using 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 hyper susceptibility of the bacteria. Overexpression of wild type ε subunit caused resistance. These results suggest that the drug also targets the ε subunit.