Fluoroquinolone resistance and mutation profiles in Mycobacterium tuberculosis through whole genome sequencing in Fujian province, China

Objective This study aimed to characterize fluoroquinolone (FQs) resistance and associated gene mutations in Mycobacterium tuberculosis (MTB) isolates from Fujian Province, with the goal of providing evidence to support precise prevention and control strategies for drug-resistant tuberculosis (TB). Methods A retrospective analysis was performed on 150 clinical MTB isolates collected from drug resistance surveillance sites. Phenotypic drug susceptibility testing (pDST) for FQs was conducted using the proportion method on solid Löwenstein–Jensen (L–J) media. In parallel, whole-genome sequencing (WGS) was applied to identify resistance-associated gene mutations. Results The overall phenotypic resistance rate to FQs was 12.7%, increasing markedly to 26.7% among multidrug-resistant (MDR) strains. The isolates were mainly classified into lineage L2 (60.0%) and L4 (38.7%), with no statistically significant association observed between lineage distribution and drug resistance profiles. Mutations linked to FQs resistance were predominantly identified in the gyrA gene (81.8%), primarily occurring at codons 90, 91, and 94. Notably, mutations were also detected in seven phenotypically susceptible isolates. Conclusion FQs resistance among MTB isolates in this study is considerable, with a particularly high burden in MDR strains. Resistance is mainly driven by single-point mutations in the gyrA gene. Importantly, WGS demonstrates potential for identifying resistance-associated mutations even in phenotypically susceptible isolates, offering valuable insights for early warning of emerging drug resistance and optimization of treatment strategies for MDR/RR-TB

Drug resistance · Gene · Genotype · Mutation · Mycobacterium tuberculosis · Tuberculosis · Whole genome sequencing · Diagnosis and treatment of tuberculosis · Mycobacterium research and diagnosis · Tuberculosis Research and Epidemiology