Whole-Genome Sequence-Based Characterization of Pre-XDR M. tuberculosis Clinical Isolates Collected in Kazakhstan

Abstract

Background: Kazakhstan has a high burden of multidrug-resistant tuberculosis in the Central Asian region. This study aimed to perform genomic characterization of Mycobacterium tuberculosis strains obtained from Kazakhstani patients with pre-extensively drug-resistant tuberculosis diagnosed in Kazakhstan. Methods: Whole-genome sequencing was performed on 10 pre-extensively drug-resistant M. tuberculosis strains from different regions of Kazakhstan. All strains had high-confidence resistance mutations according to the resistance grading system previously established by the World Health Organization. The genome analysis was performed using TB-Profiler, Mykrobe, CASTB, and ResFinder. Results: Valuable information for understanding the genetic diversity of tuberculosis in Kazakhstan can also be obtained from whole-genome sequencing. The results from the Phenotypic Drug Susceptibility Testing (DST) of bacterial strains were found to be consistent with the drug resistance information obtained from genomic data that characterized all isolates as pre-XDR. This information can help in developing targeted prevention and control strategies based on the local epidemiology of tuberculosis. Furthermore, the data obtained from whole-genome sequencing can help in tracing the transmission pathways of tuberculosis and facilitating early detection of outbreaks. Conclusions: The results from whole-genome sequencing of tuberculosis clinical samples in Kazakhstan provide important insights into the drug resistance patterns and genetic diversity of tuberculosis in the country. These results can contribute to the improvement of tuberculosis control and management programs in Kazakhstan.

Genomic Characterization of Drug-Resistant Mycobacterium tuberculosis L2/Beijing Isolates from Astana, Kazakhstan

“…Only a handful of regional studies have used the WGS approach to characterize the MTBC population in Kazakhstan. The sample size in these studies usually does not exceed 10 isolates due to budget constraints and/or lack of funding [8,9,11,12,28,29]. As a result, WGS technology has not been widely adopted in Kazakhstan in clinical or other settings.…”

“…The extensive transmission of drug-resistant strains could potentially lead to community outbreaks. To check this possibility, we analyzed transmission patterns by considering a maximum distance of 12 SNPs between the Mtb isolates as a possible epidemiological link between TB cases [28]. Although all samples were collected in the same region (Astana, Kazakhstan), only three pairs of isolates were closely related to each other and possibly linked epidemiologically, as revealed from the pairwise distance matrix (#5264-1561, #6616-3775, and #5219-5099) (Figure S2).…”

Prevalence of Beijing Central Asian/Russian Cluster 94-32 among Multidrug-Resistant M. tuberculosis in Kazakhstan

“…For example, whole-genome sequencing data of M. tuberculosis isolates from high TB-burden countries showed 23 novel katG mutations in isoniazid-resistant isolates [40] and mutations outside of the rpoB gene in rifampicin-resistant isolates [41,42]. Yet, genomic data of MDR, pre-XDR and XDR strains from Kazakhstan identified new genetic variants that may play an important role in the formation of drug resistance [24,25,41].…”

“…In Kazakhstan, studies were carried out to investigate mutations in the M. tuberculosis genes responsible for drug resistance to various antibiotics [20,21]. Several studies were performed on the molecular genotyping [22,23] and whole-genome sequencing of M. tuberculosis [24][25][26]. However, Beijing genotype clusters and their association with mutations in drug-resistant genes have not been fully investigated.…”

Draft genome sequence of a multidrug-resistant Mycobacterium tuberculosis clinical isolate, 3184-KZ

“…According to the report, Kazakhstan is among the 30 countries with the highest rates of MDR-TB. Whole-genome sequencing (WGS) and other molecular techniques for TB control were recently implemented in Kazakhstan ( 3 – 9 ).…”