Identification of genetic determinants of bedaquiline resistance in Mycobacterium tuberculosis in Ural region, Russia

Author:

Umpeleva Tatiana1ORCID,Chetverikova Elena1,Belyaev Danila12,Eremeeva Natalya1,Boteva Tatiana1,Golubeva Ludmila1,Vakhrusheva Diana1,Vasilieva Irina3

Affiliation:

1. Department of Microbiology and Preclinical Research, National Medical Research Center of Phthisiopulmonology and Infection Disease, Yekaterinburg, Russia

2. Laboratory of Medical Chemistry, Postovsky Institute of Organic Synthesis, Ural Branch of the Russian Academy of Sciences, Yekaterinburg, Russia

3. Administration, National Medical Research Center of Phthisiopulmonology and Infection Disease, Moscow, Russia

Abstract

ABSTRACT Collecting data on rare Mycobacterium tuberculosis ( Mtb ) clinical isolates with resistance to the new anti-tuberculosis drug bedaquiline is an important task for improving antimicrobial susceptibility testing methods. Nanopore whole genome sequencing, the proportion method on Middlebrook 7H11 medium, and BACTEC MGIT 960 assays were used to analyze genotypic and phenotypic resistance to bedaquiline. We found four mutations: atpE I66M, atpE А63Р, Rv0678 А36Т, and Rv0678 S53P in five isolates with different levels of phenotypic bedaquiline resistance. IMPORTANCE Bedaquiline (BDQ) is a new anti-tuberculosis drug. The phenotypic and genotypic data describing the mechanism of drug resistance are critical for the design of rapid and accurate diagnostic tests. We consider that our work, which describes genotypic and phenotypic resistance to BDQ, can contribute to the standardization of drug susceptibility testing.

Publisher

American Society for Microbiology

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