High Prevalence of atpE Mutations in Bedaquiline-Resistant Mycobacterium tuberculosis Isolates, Russia

• DOI: 10.3201/eid3103.241488
• Publication Date: 2025-02-21T22:57:16Z
• Authors: Danila Zimenkov; Anastasia Ushtanit; Elizaveta Gordeeva; Elena Guselnikova; Yakov Schwartz; Natalia Stavitskaya
• Keywords: Bedaquiline

Bedaquiline is a cornerstone drug for treating drug-resistant tuberculosis. We analyzed 11 isolates from 9 patients who were treated with bedaquiline-based regimen and remained culture-positive long after treatment start. In 4 of 8 resistant isolates, we found substitutions in AtpE, which encodes subunit c the Mycobacterium tuberculosis ATP synthase rarely identified clinical isolates. Ile66Met Glu61Asp 2 cases each. Additional mutations mmpL5, mmpL4, atpB genes could affect susceptibility to bedaquiline. MmpL5(Asn772Thr) emerged during bedaquiline treatment, whereas AtpB(Val165Leu) was 1 case simultaneously loss-of-function mmpR5 mutation susceptible strain. The mmpL4 efflux gene mixed state, pointing ongoing selection bedaquiline-resistant isolate. Another emergence mutation, accompanied by proportional increase MIC, retrospective analysis genomes