Analyzing the distribution of virulence factors of <i>Mycobacterium tuberculosis</i> and the impact of virulence gene mutations on treatment outcomes in different lineages using whole-genome sequencing in Urumqi

This study centers on Urumqi, utilizing whole-genome sequencing and comparative genomics, we explored virulence factor mutations in different <i>Mycobacterium tuberculosis</i> lineages and their impact on tuberculosis patient prognosis. We utilized routine national drug resistance surveillance data from Urumqi, gathering demographic, epidemiological, and clinical data of patients with tuberculosis between 1 January 2017 to 31 December 2021. Whole-genome sequencing was employed, followed by bioinformatics analysis using various methods and statistical models. A total of 457 patients with tuberculosis were analyzed. Through whole-genome sequencing and bioinformatics analysis, we categorized these strains into three lineages: Lineage2 (347), Lineage3 (37), and Lineage4 (73), identifying 71 virulence factor mutations. The mutation rates of virulence factors in <i>M. tuberculosis</i> exhibited polarization. Significant differences in virulence factor mutation rates were observed among different <i>M. tuberculosis</i> lineages (all <i>p</i> values < 0.05). Additionally, mutations in espE, fadE29, and mbtI genes among Lineage2 patients were considered as risk factors influencing treatment outcomes (all <i>p</i> values < 0.05), with odds ratios of 13.6200 (1.7285-107.3201), 7.1262 (1.3294-38.1997), and 14.8340 (1.1577-190.0784), respectively. Varied virulence factor mutations and virulence factor-related gene mutations exist across different <i>M. tuberculosis</i> lineages. Mutations in the espE, fadE29, and mbtI genes are risk factors that significantly affect the treatment outcome of Lineage2 patients. This finding serves as a reference for investigating the future evolutionary direction, transmissibility, drug resistance, and pathogenicity of <i>M. tuberculosis</i> virulence factors in regions with diverse lineages and frequent population movements.