Abstract: Objective To understand the drug resistance of tuberculosis patients in Xi'an, and to analyze the mutation characteristics of drug-resistant genes related to Mycobacterium tuberculosis （MTB） that are resistant to commonly anti-tuberculosis drugs. Methods The sputum samples of tuberculosis patients with positive sputum smears reported by tuberculosis-designated hospitals in Xi'an from January to December 2020 were isolated and cultured, and the samples identified as MTB-positive strains were tested for drug sensitivity, and the mutation characteristics of drug-resistant related genes of drug-resistant strains were analyzed by whole genome sequencing （WGS）. Results A total of 892 MTB-positive patients were identified, including 758 newly treated patients and 134 retreated patients; 209 cases were drug-resistant, and the total drug resistance rate was 23.43%; The rates of monodrug resistant tuberculosis （MR-TB）, poly-drug resistant tuberculosis （PDR-TB）, multidrug-resistant tuberculosis （MDR-TB）, extensive drug-resistant tuberculosis （XDR-TB）, and rifampicin-resistant tuberculosis （RR-TB） were 10.43%, 2.47%, 4.60%, 0.45%, and 6.28%, respectively. The drug resistance rate of retreated patients （31.34%） was significantly higher than that of newly treated patients （22.03%）; The proportion of MR-TB, PDR-TB, MDR-TB, XDR-TB, and RR-TB in drug-resistant patients of the two groups was statistically significant （all P<0.05）. Among 209 MTB-resistant strains, the mutations of resistance-related genes to commonly used anti-tuberculosis drugs were 81 strains of katG （77.14%, isoniazid）, 54 strains of rpoB （96.43%, rifampicin）, 49 strains of rpsL （84.48%, streptomycin）, 24 strains of embB （88.89%, ethambutol）, 17 strains of pncA （89.47%, pyrazinamide）, 10 strains of gyrA （90.91%, ofloxacin）, and 18 strains of rss （94.74%, second-line injection type anti-tuberculosis drugs）. Among them, katG S315T （72 strains）, rpsL K43R （42 strains）, rss A1401G （23 strains）, rpoB S531L （19 strains）, embB M306V （13 strains）, and rpoB H526D （11 strains） had the highest mutation frequency of related drug resistance genes. Conclusions Tuberculosis patients in Xi'an are highly resistant to commonly used anti-tuberculosis drugs. The gene mutations of drug-resistant strains are mainly katG, rpoB, rpsL, embB, and pncA, and mainly occur at high-frequency mutation sites such as katG S315T and rpsL K43R. It is theoretically feasible to develop sensitive and specific rapid molecular detection methods based on the above mutation characteristics.

Key words: Tuberculosis, Mycobacterium tuberculosis, Drug resistance, Whole genome sequencing, Gene mutation