P074

1:National Center for Biotechnology, Astana, Kazakhstan; 2:City Center for Phthisiopulmonology of the Akimat of Astana, Astana, Kazakhstan; 3:National Scientific Center for Phthisiopulmonology, Almaty, Kazakhstan; 4:Université Paris-Saclay, Paris, France

Kazakhstan remains one of the 30 countries with the highest burden of multidrug-resistant tuberculosis (MDR-TB), primarily driven by the circulation of L2/Beijing M. tuberculosis strains within the Central Asian/Russian cluster. We conducted whole-genome sequencing (WGS) of 177 clinical L2/Beijing isolates of M. tuberculosis obtained from 15 regions of Kazakhstan, including several major urban centers. Whole-genome sequencing and SNP-based classification, according to the nomenclature proposed by Thawornwattana, revealed that the majority of M. tuberculosis L2/Beijing isolates belonged to sublineage Central Asia outbreak (L2.2.M4.9.1) (119; 67.23%), followed by L2.2.M4.9 (44; 24.86%), Europe/Russia W148 outbreak (L2.2.M4.5) (11; 6.21%), Clade A (L2.2.M4.9.2) (2; 1.13%), and sublineage L2.2.M4 (1; 0.56%). Phenotypic drug susceptibility testing indicated a high proportion of multidrug-resistant (MDR) isolates (n =83; 46.89%) and pre-extensively drug-resistant (pre-XDR) isolates (n = 26; 14.69%). Additionally, an extensively drug-resistant (XDR) isolate (n = 1; 0.56%) was detected in the study population. Our findings demonstrate the predominance of the L2.2.M4.9.1 (Central Asia outbreak, CAO) sublineage among circulating L2/Beijing M. tuberculosis strains in Kazakhstan and reveal a substantial burden of drug resistance, including MDR, pre-XDR, and XDR phenotypes. These results provide insights into the population structure and resistance patterns of M. tuberculosis in the region, emphasizing the importance of integrating genomic surveillance into national TB control strategies.