Genomic Characterization of Drug-Resistant Mycobacterium tuberculosis L2/Beijing Isolates from Astana, Kazakhstan

Auganova D. Atavliyeva S. Amirgazin A. Akisheva A. Tsepke A. Tarlykov P.
October 2023 Multidisciplinary Digital Publishing Institute (MDPI)

Antibiotics
2023 #12 Issue 10

Kazakhstan ranks among the countries with the highest number of MDR-TB patients per 100,000 population worldwide. The successful transmission of local MDR strains of Mycobacterium tuberculosis (Mtb) poses a significant threat to disease control. In this study, we employed whole-genome sequencing to examine drug resistance, compensatory mutations, population structure, and transmission patterns in a sample of 24 clinical isolates of L2/Beijing Mtb collected in Astana, Kazakhstan between 2021 and 2022. The genotypic prediction of Mtb susceptibility to anti-TB agents was consistent with the phenotypic susceptibility, except for bedaquiline. An analysis of resistance-associated genes characterized most of the isolates as pre-extensively drug-resistant tuberculosis (pre-XDR-TB) (n = 15; 62.5%). The phylogenetic analysis grouped the isolates into four transmission clusters; the dominant cluster was assigned to the “aggressive” Central Asia outbreak (CAO) clade of L2/Beijing (n = 15; 62.5%). Thirteen mutations with putative compensatory effects were observed exclusively in Mtb isolates containing the rpoB S450L mutation. The putative compensatory mutations had a stabilizing effect on RpoABC protein stability and dynamics. The high prevalence of the CAO clade in the population structure of Mtb may explain the rapid spread of MDR-TB in Kazakhstan.

compensatory mutations , drug resistance , genetic diversity , Kazakhstan , Mycobacterium tuberculosis , whole-genome sequencing

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National Center for Biotechnology, Astana, 010000, Kazakhstan
City Center for Phthisiopulmonology of the Akimat of Astana, Astana, 010000, Kazakhstan

National Center for Biotechnology
City Center for Phthisiopulmonology of the Akimat of Astana

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