Whole-genome sequencing for analyzing the transmission characteristics of drug-resistant Mycobacterium tuberculosis in Ganzhou, China.

OBJECTIVE: The study aimed to understand the drug resistance profile and transmission characteristics of drug-resistant Mycobacterium tuberculosis (MTB) in Ganzhou, China, to provide a scientific basis for developing prevention and control strategies. METHODS: DNA extracted from re-cultured positive strains underwent whole-genome sequencing (WGS). The online platform SAM-TB was used to identify drug resistance-related mutations in each strain, construct a phylogenetic tree, and calculate the pairwise strain single-nucleotide polymorphism (SNP) distances. A threshold of 12 SNPs between pairwise strains was set to identify transmission clusters. Epidemiological investigations were conducted for patients within these transmission clusters to analyze the characteristics of drug-resistant tuberculosis (TB) transmission. RESULTS: A total of 82 strains were analyzed. The most common mutations observed for isoniazid, rifampicin, ethambutol, and streptomycin were katG (S315T, 32/61), rpoB (S450L, 13/37), embB (M306V, 5/12), and rpsL (K43R, 18/26), respectively. Mutations were also observed in genes conferring resistance to other drugs, including pncA (pyrazinamide), gyrA (ofloxacin), rrs, and eis (aminoglycosides). The strains belonged to lineage 2 (75.61%, 62/82) and 4 (24.39%, 20/82). Three clusters containing 12 drug-resistant strains were identified as transmission clusters, ranging in size from 2 to 8, with a clustering rate of 14.63% (12/82). Notably, lineage 2 strains were more prevalent in clustered cases than lineage 4 strains (19.35%, 12/62 vs. 0%, 0/20, Fisher’s exact test, P = 0.033). The isoniazid resistance rate was significantly higher in clustered strains (100%, 12/12) than in non-clustered strains (70.00%, 49/70) (Fisher’s exact test, P = 0.031). Two potential transmission chains of drug-resistant TB were identified. CONCLUSION: This study utilized WGS technology to provide important data on the genetic mutation types and transmission dynamics of drug-resistant TB in Ganzhou. WGS demonstrates significant potential in early prediction of drug resistance in TB and identification of recent transmission events, offering essential support for monitoring public health events and intervening in drug-resistant tuberculosis.