In Kazakhstan, the total incidence rate of tuberculosis in 2021 was 74 cases per 100,000 population. The aim of this study was the characterization of drug-resistant (DR) M. tuberculosis (MTB) collected in Kazakhstan and to perform pilot whole genome sequencing for drug resistance detection.

Drug susceptibility testing to first/second-line anti-TB drugs was done by using the BACTEC MGIT-960 system for 144 clinical isolates. Pilot whole genome sequencing (WGS) was performed by using MiSeq (Illumina) platform for 22 clinical isolates of M. tuberculosis. Data analysis and variant detection were performed using the MTBseq pipeline. The genome analysis for DR was performed using programs TB-Profiler, Mykrobe, CASTB, and ResFinder.

A characterized collection of 144 samples of DR M. tuberculosis clinical isolates was prepared, of which 123 (85.42%) with different drug resistance profiles and susceptible ? 21 (14.58%). We concentrated on SNPs in genes known to confer resistance to first- and second-line anti-TB and made a detailed analysis of pre-XDR strains. A comparison of phenotypic and genomic drug susceptibility testing results identified some differences in the resistance patterns of the isolates. Para-aminosalicylic acid exhibited susceptibility against most isolates, suggesting that it could be a promising treatment option. All the isolates were classified as the Beijing genotype regarding the genomic analysis.

Kazakhstan started the process of implementing NGS for drug resistance detection, and this study help to understand the role of WGS in diagnosing DR TB.

Grant references: This research was funded by NU CRP grant ?11022021CRP1511