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Genetic Diversity and Drug Resistance Profiles of Mycobacterium tuberculosis L2/Beijing Isolates in Kazakhstan: Insights from Whole-Genome Sequencing

P Tarlykov(1) D Auganova(1) S Atavliyeva(1) A Akisheva(2) A Tsepke(2) Y Skiba(1)

1:National Center for Biotechnology; 2:City Center for Phthisiopulmonology of the Akimat of Astana

Kazakhstan is among the 30 countries with a high burden of multidrug-resistant tuberculosis (MDR-TB). The prevalence of drug-resistant isolates in Kazakhstan is linked to the Central Asian/Russian cluster of the L2/Beijing family of Mycobacterium tuberculosis. A total of 102 L2/Beijing clinical isolates of M. tuberculosis representing various regions in Kazakhstan, including Aktau and Kostanay (n = 13); Kyzylorda (n = 12); Taldykourgan (n = 11); Semey (n = 9); Aktobe (n = 7); Atyrau, Karaganda, and Pavlodar (n = 6); Stepnogorsk, and Uralsk (n = 5); Almaty, and Taraz (n = 4); and Shymkent (n = 1) were selected for whole-genome sequencing (WGS). The sequenced L2/Beijing isolates were characterized according to a recent SNP-based nomenclature proposed by Thawornwattana. Most of the studied M. tuberculosis isolates were assigned to the L2.2.M4.9.1 sublineage (n = 69; 67.64%), also known as the Central Asia outbreak. Other sublineages were represented by Central Asia L2.2.M4.9 (n = 27; 26.47%), Europe/Russia W148 outbreak L2.2.M4.5 (n = 5, 4.90%), and L2.2.M4 sublineage (n = 1; 0.98%).  Multidrug-resistant (n = 60) and pre-extensively drug-resistant (n = 7) isolates were prevalent in the sample, based on phenotypic and WGS data. Notably, the Central Asia outbreak and Europe/Russia W148 outbreak strains are associated with the outbreaks of MDR-TB in Central Asia. This ongoing research is focused on drug-resistance profiles, genotypes, and transmission dynamics among different regions of Kazakhstan using next-generation sequencing, followed by bioinformatics analysis employing the TB-Annonator pipeline.

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