Prevalence of the epidemic variants of the Mycobacterium tuberculosis Beijing genotype across Russian regions

Russia is a TB high-burden country with steadily increasing MDR-TB rate (30% among new cases). We aimed to analyze the genetic structure of the clinically and epidemiologically significant subtypes of ancient and modern sublineages of the <i>M. tuberculosis</i> Beijing genotype in different regions of Russia. M. tuberculosis clinical isolates (n=1042) from Russian regions (Northwest, Ural, Siberia, Far East) were tested by genotyping and analysis of subtype/sublineage specific markers of the Beijing genotype. The Beijing genotype was dominant in all studied regions (50-72%), and was associated with MDR compared to non-Beijing genotypes (p=0.0003). The Beijing 94-32-cluster (=Central-Asian/Russian clade) was overall dominant (21-48%), but was significantly less MDR than Beijing B0/W148-cluster (=Russian epidemic clone) (p=0.02). The highest rate of the 94-32-cluster in Omsk, West Siberia may be due to its proximity to Kazakhstan. B0/W148 predominates in Siberia (up to 70%), its likely region of origin. The Beijing early ancient sublineage 2 (del_RD181) is mainly found in European Russia and Siberia, while early ancient sublineage 1 (intact RD181) dominates in Buryatia, Far East, at 16%. Noteworthy, both major VNTR clusters within ancient Beijing were strongly associated with MDR and XDR. To conclude, highly drug-resistant and genetically diverse strains of the <i>M. tuberculosis</i> Beijing genotype circulate in different regions of Russia and new resistant clones appear emerging. This emphasizes the importance of their permanent monitoring that is critical for timely tracing of spread and emergence of new resistant variants. Supported by Russian Science Foundation (grant 19-14-00013).