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

Abstract

This study centers on Urumqi, utilizing whole-genome sequencing and comparative genomics, we explored virulence factor mutations in different Mycobacterium tuberculosis 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 M. tuberculosis exhibited polarization. Significant differences in virulence factor mutation rates were observed among different M. tuberculosis lineages (all p values  < 0.05). Additionally, mutations in espE, fadE29, and mbtI genes among Lineage2 patients were considered as risk factors influencing treatment outcomes (all p 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 M. tuberculosis 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 M. tuberculosis virulence factors in regions with diverse lineages and frequent population movements.