WHOLE GENOME SEQUENCING AND GENETIC CHARACTERIZATION OF DIFFERENT DRUG-RESISTANT M.TUBERCULOSIS CLINICAL ISOLATES FROM KAZAKHSTAN

Abstract

Tuberculosis (TB) remains one of the most prevalent infectious diseases globally and is the second leading cause of death from an infectious agent after COVID-19. Mycobacterium tuberculosis (Mtb), the causing agent of TB, was responsible for an estimated 7.5 million new cases and 1.3 million deaths worldwide in 2022. Despite advancements in antibiotic development, the emergence of multidrug-resistant (MDR) Mtb strains, including pre-extensively drug-resistant (pre-XDR) and extensively drug-resistant (XDR) strains, poses significant challenges to TB treatment. This study performed whole-genome sequencing (WGS) to analyze 186 Mtb isolates from Kazakhstani patients diagnosed with pre-XDR and XDR TB. Using the Illumina next-generation sequencing (NGS) platform, this research identifies genetic variants associated with drug resistance and determines genes contributing to drug-resistant phenotypes. While extensive WGS-based studies on drug-resistant Mtb strains have been conducted globally, data from Kazakhstan remain limited. This work provides critical insights into the mutation specter and genetic diversity of pre-XDR and XDR Mtb strains in Kazakhstan, contributing to the understanding of regional drug resistance mechanisms and informing targeted TB control strategies.