Genetic Determinants of Drug Resistance in Mycobacterium tuberculosis Beijing B0/W148 isolates

Background: The Beijing B0/W148 is a clone variant of M. tuberculosis (MTB) that is often detected in tuberculosis patients in Russia. It has stronger association with multidrug resistance and possesses unique pathogenic properties. Objectives: To identify the spectrum of drug resistance mutations of MTB Beijing B0/W148 isolated from patient living in Ural Federal District of Russia. Material and Methods: The study included MTB Beijing B0/W148 DNA samples isolated from clinical material of 228 TB patients between 2017 and 2018 years. Drug resistance to rifampicin, isoniazid, fluoroquinolones, aminoglycosides, and capreomycin and genotype of MTB were analyzed by using microarray test system TB-TEST (BIOCIP-IMB, Russia). Results: Molecular analysis identifided that 219 (96,1%) DNA samples had MDR assosiated mutations, in 212 (92,9%) cases it was combination of rpoB S531L and katG S315T1 mutations. Pre-XDR MTB prevalence rate among MDR-TB patients was 99 (43,4%). 23 (10,1%) MDR isolates were resistent to fluoroquinolones, in 15 (6,6%) it were gyrA gene mutations at 94 codon. 76 (33.3%) samples had mutations to aminoglycosides. More common mutations were: eis g10a – 32 (14,0%) and rrs a1401g – 21 (9,2%). XDR associated mutations were diagnosed in 75 (32,9%). It is interesting to note 9 samples without mutations to rifampicin. For four patients cultures on L-J medium were obtained and for three isolates drug sensibility to rifampicin by absolute concentration method were confirmed. Conclusion: We identified the high level of MDR pre-XDR and XDR associated mutations among Beijing B0/W148 clone that underlines the epidemiological and clinical danger of this genetic variant of MTB.