Insight into pathogenomics and phylogeography of hypervirulent and highly-lethal Mycobacterium tuberculosis strain cluster.

BACKGROUND: . The Mycobacterium tuberculosis Beijing genotype is globally spread lineage with important medical properties that however vary among its subtypes. M. tuberculosis Beijing 14717-15-cluster was recently discovered as both multidrug-resistant, hypervirulent, and highly-lethal strain circulating in the Far Eastern region of Russia. Here, we aimed to analyze its pathogenomic features and phylogeographic pattern. RESULTS: . The study collection included M. tuberculosis DNA collected between 1996 and 2020 in different world regions. The bacterial DNA was subjected to genotyping and whole genome sequencing followed by bioinformatics and phylogenetic analysis. The PCR-based assay to detect specific SNPs of the Beijing 14717-15-cluster was developed and used for its screening in the global collections. Phylogenomic and phylogeographic analysis confirmed endemic prevalence of the Beijing 14717-15-cluster in the Asian part of Russia, and distant common ancestor with isolates from Korea (> 115 SNPs). The Beijing 14717-15-cluster isolates had two common resistance mutations RpsL Lys88Arg and KatG Ser315Thr and belonged to spoligotype SIT269. The Russian isolates of this cluster were from the Asian Russia while 4 isolates were from the Netherlands and Spain. The cluster-specific SNPs that significantly affect the protein function were identified in silico in genes within different categories (lipid metabolism, regulatory proteins, intermediary metabolism and respiration, PE/PPE, cell wall and cell processes). CONCLUSIONS: . We developed a simple method based on real-time PCR to detect clinically significant MDR and hypervirulent Beijing 14717-15-cluster. Most of the identified cluster-specific mutations were previously unreported and could potentially be associated with increased pathogenic properties of this hypervirulent M. tuberculosis strain. Further experimental study to assess the pathobiological role of these mutations is warranted.

Epidemiology and Drug Resistance Patterns of Mycobacterium tuberculosis in High-Burden Area in Western Siberia, Russia.

Russia is a high-burden area for multidrug-resistant tuberculosis (MDR-TB). Here, we studied the epidemiological situation and drug resistance patterns of Mycobacterium tuberculosis in the Omsk region in Western Siberia. M. tuberculosis isolates (n = 851) were recovered from newly diagnosed TB patients in 2021. The isolates were tested by bacteriological and molecular methods, and long-term epidemiological data were analyzed. The TB incidence dec, this is not variablereased from 93.9 in 2012 to 48.1 in 2021, per 100,000 population, but the primary MDR-TB rate increased from 19.2% to 26.4%. The destructive forms of tuberculosis accounted for 37.8% of all cases, while 35.5% of patients were smear-positive. Of all isolates tested, 55.2% were culture-positive, of which 94.5% were further tested for phenotypic drug resistance and associated mutations. More than half (53.4%) of isolates were drug-resistant, 13.9% were monoresistant and 67.9% were MDR. Among MDR isolates, 40.4% were pre-XDR, and 19.2% were XDR. The spectrum of drug resistance included second-line drugs (new-generation fluoroquinolones, linezolid), which significantly increase the risk of an adverse outcome in patients. In conclusion, our results highlight the critical importance of monitoring drug resistance in circulating M. tuberculosis strains emerging due to ineffective treatment and active transmission.