Genetic diversity and transmission pattern of multidrug-resistant tuberculosis based on whole-genome sequencing in Wuhan, China.

BACKGROUND

Investigating the molecular epidemiological characteristics of multidrug-resistant tuberculosis (MDR-TB) in China's moderate-burden regions, such as Wuhan, is crucial for understanding and controlling disease transmission.

MATERIALS AND

METHODS

This study analyzed MDR-TB isolates from pulmonary tuberculosis cases registered at Wuhan Pulmonary Hospital in 2017. Whole genome sequencing (WGS) was used to identify resistance-conferring mutations, examine their associations with specific Mycobacterium tuberculosis lineages or sublineages, and assess clustering profiles.

RESULTS

Among the 149 analyzed strains, the most prevalent mutations associated with resistance to 11 anti-tuberculosis drugs were identified as follows: rpoB Ser450Leu (59.73%, rifampicin), katG Ser315Thr (62.42%, isoniazid), embB Met306Val (42.86%, ethambutol), rpsL Lys43Arg (68.13%, streptomycin), pncA Trp68Arg (10.53%, pyrazinamide), gyrA Asp94Gly (22.50%, fluoroquinolones), and rrs 1401A > G (50.00-100.00%, second-line injectable aminoglycosides). Additional mutations were detected in fabG1 c-15C > T (42.86%, ethionamide) and thyX c-16C > T (21.43%, p-aminosalicylic acid). Notably, rare mutations absent from the WHO mutation catalog, such as ahpC c-52C > T and rpsL Lys43Thr, were also observed. The mutation frequency of embB Met306Ile was significantly higher in Lineage 4 (L4) strains than in Lineage 2 (L2) strains (p = 0.0150), while the rpsL Lys43Arg mutation frequency was lower in L4 compared to L2 (p = 0.0333). A total of 31 MDR MTB Mycobacterium tuberculosis isolates formed clusters, resulting in a clustering rate of 20.81% and a recent transmission rate of 11.41%. The clustering rates between L4 and L2 strains were not significantly different (χ2 = 0.0017, p > 0.05).

CONCLUSION

The genetic diversity of MDR-TB in Wuhan demonstrates unique characteristics, with evidence of localized transmission. These findings highlight the urgent need to strengthen measures to detect early cases of MDR-TB and control transmission of MDR-TB in the region.