Abstract
Tuberculosis (TB) remains a major public health challenge in China. Meigu County, in Liangshan Yi Autonomous Prefecture, Sichuan Province, is severely affected by a high TB burden, a situation exacerbated by its geographic isolation and socioeconomic constraints. This study used DNA microarray technology to assess drug resistance in 378 Mycobacterium tuberculosis (M. tuberculosis) isolates from bronchoalveolar lavage fluid samples collected in Meigu County from 2022 to 2024. During this period, the drug resistance rates of rifampicin, isoniazid, and multidrug-resistant TB initially rose and then declined. Only the variation in isoniazid resistance reached statistical significance (χ² = 6.462, P = 0.038). Age-specific analysis revealed a significantly higher prevalence of isoniazid resistance among individuals aged 19-60 years (χ² = 7.034, P = 0.022). Whole-genome sequencing was further applied to 123 isolates collected from the same geographical area and sample type in 2024. Genomic analysis detected drug-resistant mutations in 8.9% (11/123) of the isolates, with dominant mutations including rpoB p.Ser450Leu and katG p.Ser315Thr. Lineage 2 and Lineage 4 strains demonstrated comparable prevalence, with no statistically significant difference observed among the cases analyzed in 2024. Phylogenetic clustering based on a ≤12 single-nucleotide polymorphism (SNP) threshold grouped 31.7% (39/123) of the strains into 15 distinct transmission clusters, reflecting ongoing community spread. Clustering was significantly associated with amikacin resistance (P = 0.001). Discrepancies in resistance predictions between bioinformatic tools highlighted the necessity for standardized genomic surveillance protocols. These results offer the first comprehensive genomic characterization of M. tuberculosis transmission and resistance in Meigu County, underscoring the critical need for targeted public health strategies to interrupt transmission in this high-incidence setting. IMPORTANCE: This study provided a critically important investigation into the molecular epidemiology of drug-resistant tuberculosis in Meigu County, a remote and high-burden region in Sichuan Province, China. By combining DNA microarray chip technology and whole-genome sequencing, the researchers characterized the genetic makeup, drug resistance patterns, and transmission dynamics of strains of Mycobacterium tuberculosis circulating in this underserved community. They identified specific mutations responsible for resistance to key anti-tuberculosis drugs and revealed ongoing local transmission through genomic clustering analysis. The findings highlighted the urgent need for improved public health interventions, standardized treatment protocols, and enhanced genomic surveillance in regions with limited healthcare resources. This work offered the comprehensive genomic insight into tuberculosis transmission in Meigu County and served as a model for understanding and combating drug-resistant tuberculosis in other high-incidence, economically disadvantaged areas worldwide.