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

被引:3
作者
Auganova, Dana [1 ]
Atavliyeva, Sabina [1 ]
Amirgazin, Asylulan [1 ]
Akisheva, Akmaral [2 ]
Tsepke, Anna [2 ]
Tarlykov, Pavel [1 ]
机构
[1] Natl Ctr Biotechnol, Astana 010000, Kazakhstan
[2] City Ctr Phthisiopulmonol Akimat Astana, Astana 010000, Kazakhstan
来源
ANTIBIOTICS-BASEL | 2023年 / 12卷 / 10期
关键词
Mycobacterium tuberculosis; drug resistance; compensatory mutations; Kazakhstan; whole-genome sequencing; genetic diversity; COMPENSATORY EVOLUTION; RIFAMPICIN RESISTANCE; MUTATIONS; STRAINS; TRANSMISSION; FITNESS; EPIDEMIOLOGY; DETERMINANTS; BEDAQUILINE; TOOL;
D O I
10.3390/antibiotics12101523
中图分类号
R51 [传染病];
学科分类号
100401 ;
摘要
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.
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页数:17
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