Genomic characterization of multidrug-resistant tuberculosis in Shanghai, China: antibiotic resistance, virulence and transmission

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Abstract Objectives Whole-genome sequencing (WGS) was employed to investigate antibiotic resistance, virulence and transmission profiles of multidrug-resistant tuberculosis (MDR-TB) isolates from Shanghai, China. Methods A total of 306 MDR-TB clinical isolates were collected from Shanghai Pulmonary Hospital and underwent phenotypic drug susceptibility testing (DST) for common anti-TB drugs and WGS. Combined 778 published bacterial sequences, we performed phylogenetic analysis, resistance and virulence gene identification to understand the genetic relationships and resistance mechanisms among those strains. Results WGS determination, supported by DST, revealed high resistance rates for isoniazid (83.66%) and rifampicin (90.20%) among the MDR-TB isolates. Key resistance-associated mutations included katG Ser315Thr for isoniazid, rpoB mutations for rifampicin, and embB Met306Val for ethambutol. WGS demonstrated >90% concordance with culture-based DST for most drugs, except ethambutol that showed a 76.80% concordance. Analyses of virulence factors and phylogenetics revealed the genetically homogeneous, endemic MDR-TB population in Shanghai, with no evidence of recent transmission. Conclusions This study highlights the genetic homogeneity and endemic nature of MDR-TB in Shanghai, providing insights into key resistance mechanisms of TB.

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