Extrapulmonary and, in particular, spinal tuberculosis (TB) constitutes a minor but significant part of the total TB incidence. In spite of this, almost no studies on the genetic diversity and drug resistance of Mycobacterium tuberculosis isolates from spinal TB patients have been published to date. Here, we report results of the first Russian and globally largest molecular study of M. tuberculosis isolates recovered from patients with tuberculous spondylitis (TBS). The majority of 107 isolates were assigned to the Beijing genotype ( n = 80); the other main families were T ( n = 11), Ural ( n = 7), and LAM ( n = 4). Multidrug resistance (MDR) was more frequently found among Beijing (90.5%) and, intriguingly, Ural (71.4%) isolates than other genotypes (5%; P < 0.001). The extremely drug-resistant (XDR) phenotype was exclusively found in the Beijing isolates ( n = 7). A notable prevalence of the rpoB531 and katG315 mutations in Beijing strains that were similarly high in both TBS (this study) and published pulmonary TB (PTB) samples from Russia shows that TBS and PTB Beijing strains follow the same paradigm of acquisition of rifampin (RIF) and isoniazid (INH) resistance. The 24-locus mycobacterial interspersed repetitive unit–variable-number tandem-repeat (MIRU-VNTR) subtyping of 80 Beijing isolates further discriminated them into 24 types (Hunter Gaston index [HGI] = 0.83); types 100-32 and 94-32 represented the largest groups. A genotype of Russian successful clone B0/W148 was identified in 30 of 80 Beijing isolates. In conclusion, this study highlighted a crucial impact of the Beijing genotype and the especially prominent role of its MDR-associated successful clone B0/W148 cluster in the development of spinal MDR-TB in Russian patients.

The Beijing genotype is the main family of Mycobacterium tuberculosis in Russia. We analyzed its diversity and drug resistance in provinces across Northwestern Russia to identify the epidemiologically relevant Beijing strains. The study collection included 497 isolates from newly-diagnosed tuberculosis (TB) patients. Bacterial isolates were subjected to drug-susceptibility testing and genotyping. The Beijing genotype was detected in 57.5% (286/497); 50% of the Beijing strains were multidrug-resistant (MDR). Central Asian/Russian and B0/W148 groups included 176 and 77 isolates, respectively. MDR was more frequent among B0/W148 strains compared to Central Asian/Russian strains (85.7% vs. 40.3%, p < 0.0001). Typing of 24 minisatellite loci of Beijing strains revealed 82 profiles; 230 isolates were in 23 clusters. The largest Central Asian/Russian types were 94-32 (n = 75), 1065-32 (n = 17), and 95-32 (n = 12). B0/W148 types were 100-32 (n = 59) and 4737-32 (n = 5). MDR was more frequent in types 1065-32 (88.2%), 100-32 (83.1%), and 4737-32 (100%). In contrast, type 9391-32 (n = 9) included only drug-susceptible strains. To conclude, M. tuberculosis Beijing genotype is dominant in Northwestern Russia, and an active transmission of overwhelmingly MDR B0/W148 types explains the reported increase of MDR-TB. The presence of MDR-associated minor variants (type 1071-32/ancient Beijing and Central Asia Outbreak strain) in some of the studied provinces also requires attention.

Видовое разнообразие нетуберкулезных микобактерий у больных микобактериозом на территориях Северо-Западного федерального округа России

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This study aimed to determine phenotypic and genotypic drug resistance patterns of Mycobacterium tuberculosis strains from children with tuberculosis (TB) in China and Russia, two high-burden countries for multi/extensively-drug resistant (MDR/XDR) TB. Whole-genome sequencing data of M. tuberculosis isolates from China (n = 137) and Russia (n = 60) were analyzed for phylogenetic markers and drug-resistance mutations, followed by comparison with phenotypic susceptibility data. The Beijing genotype was detected in 126 Chinese and 50 Russian isolates. The Euro-American lineage was detected in 10 Russian and 11 Chinese isolates. In the Russian collection, the Beijing genotype and Beijing B0/W148-cluster were dominated by MDR strains (68% and 94%, respectively). Ninety percent of B0/W148 strains were phenotypically pre-XDR. In the Chinese collection, neither of the Beijing sublineages was associated with MDR/pre-XDR status. MDR was mostly caused by low fitness cost mutations (rpoB S450L, katG S315T, rpsL K43R). Chinese rifampicin-resistant strains demonstrated a higher diversity of resistance mutations than Russian isolates (p = 0.003). The rifampicin and isoniazid resistance compensatory mutations were detected in some MDR strains, but they were not widespread. The molecular mechanisms of M. tuberculosis adaptation to anti-TB treatment are not unique to the pediatric strains, but they reflect the general situation with TB in Russia and China.