Key impact of Beijing strains including new resistant clusters on spread of multidrug-resistant tuberculosis in northern Russia

Northern Russia is characterized by socio-environmental conditions contributing to the spread of tuberculosis (TB) and a high ~30% rate of primary multidrug-resistant (MDR) TB. We applied high-resolution molecular methods to study the Mycobacterium tuberculosis population in the Arkhangelsk region of Northern Russia. All available M. tuberculosis isolates recovered from newly diagnosed patients from January to December 2018 ( n = 88) were genotyped using 24-loci MIRU-VNTR, spoligotyping, and, partly, by whole-genome sequencing (WGS). The population structure revealed a predominance of the Beijing genotype and Euro-American lineage, with significant drug resistance burden associated with Beijing and its B0/W148 strain. Beijing strains showed a significantly higher association with MDR and pre-extensively drug-resistant (pre-XDR) TB compared to non-Beijing strains ( P = 0.0013). All Beijing B0/W148 isolates were MDR, whereas the majority (71.4%) of Beijing Central Asian/Russian subtype strains were drug-sensitive. WGS analysis of newly discovered Beijing clusters 3828-32 and 10167-32 in this area indicated a historical transmission over several decades, reflecting long-term endemic circulation. The presence of compensatory mutations in rpoC among MDR strains suggests enhanced fitness facilitating their ongoing transmission. An intriguing cluster of recent transmission of a non-Beijing strain (spoligotype SIT53, L4.8 sublineage) was identified through combined epidemiological and genomic investigation. To conclude, the prevalence of Beijing strains rose from 39.3% in 1998 to 67.0% ( P P = 0.097). This highlights the key role of MDR Beijing strains, including new resistant clusters, in disseminating MDR-TB in the region and the importance of continuous surveillance using high-resolution genotyping.IMPORTANCEThe Arkhangelsk region is the largest province of northern European Russia. One-third of newly diagnosed tuberculosis patients are infected with multidrug-resistant (MDR) Mycobacterium tuberculosis strains. We assessed the molecular population structure of M. tuberculosis in the Arkhangelsk region in the COVID-19 pre-pandemic year 2018. We identified important MDR clusters and elucidated tuberculosis transmission patterns. An intriguing cluster of recent transmission was identified through the combined use of epidemiological investigation and whole-genome sequencing. The prevalence of Beijing genotype strains increased from 39.3% in 1998 to 67.0%, and the Russian epidemic MDR strain B0/W148 doubled from 11.2% in 1998 to 20.5%. Furthermore, we described new MDR clusters emerging within the Beijing genotype. This highlights the key impact of the MDR Beijing strains and the importance of continuous surveillance using high-resolution genotyping. This study of the pre-pandemic strain collection provides an indispensable intermediate time point between earlier studies carried out 25 years ago and ongoing surveillance.