genotypic characterization of katg, inha, and ahpc in isoniazid-resistant mycobacterium tuberculosis clinical isolates in shanghai, china

Background:mycobacterium tuberculosis is a pathogen that causes tuberculosis and can invade various organs in infected patients. its high morbidity and high mortality seriously threaten human health. in recent years, the continuous emergence of drugresistant tuberculosis bacteria has brought severe challenges to the prevention and control of tuberculosis.objectives:this study aimed to characterize the most frequent mutations of the katg, inha, and ahpc genes in isoniazid (inh)resistant m. tuberculosis clinical isolates in shanghai pulmonary hospital, china, and investigate the relationship between gene mutations and the minimum inhibitory concentrations (mics) of inh against m. tuberculosis.methods:we collected 92 inhresistant and 30 inhsusceptible clinical isolates of m. tuberculosis. the drug resistance profiles of m. tuberculosis clinical isolates against common antituberculosis drugs were determined and sequencing analysis was performed.results:of 92 inhresistant strains, mutations in the katg and inha genes were observed in 64 (69.6%) isolates and five (5.4%) isolates, respectively, and only had one (1.1%) strain both katg and inha mutations. among them, 62 (67.4%) strains carried a single mutation at codon 315 of the katg gene and a new mutation site was found in the katg gene of two strains. we detected a single mutation site at codon 271 and three simultaneous mutation sites at codons 315, 431, and 439. only one (3.3%) of the 30 isoniazidsensitive strains had the katg mutation. the ahpc mutation was detected in no experimental strains. the katg ser 315 thr (agc315acc) mutation occurred in 53 (68.8%) out of 77 strains with high mics (≥ 1 g/ml) of isoniazidresistant m. tuberculosis while five (33.3%) out of 15 strains with low mics (less than 1 g/ml) had katg ser 315 thr (agc315acc) mutation.conclusions:isoniazidresistant strains were dominated by ser315 → thr (agc → acc) substitution, which seems to be associated with multidrug resistance and highlevel resistance to inh. multisite mutations are related to multidrugresistant m. tuberculosis and the discovery of new mutation sites provides a new basis for the detection of drugresistant m. tuberculosis.