Objective: Drug-resistant tuberculosis is a major public health problem, especially in the southern region of Xinjiang, China; however, there is little information regarding drug resistance profiles and mechanism of Mycobacterium tuberculosis  in this area. The aim of this study was to determine the prevalence and molecular characteristics of M. tuberculosis  resistant to four anti-tuberculosis drugs from this area.
Methods: Three hundred and forty-six isolates from the southern region of Xinjiang, China were included and used to perform phenotypic drug susceptibility testing and whole genome sequencing (WGS). Mutations in seven loci associated with drug resistance, including rpoB  for rifampicin (RMP), katG, inhA  promoter and oxyR-ahpC  for isoniazid (INH), rrs  530 and 912 loops and rpsL  for streptomycin (STR), and embB  for ethambutol (EMB), were characterized.
Results: Among 346 isolates, 106, 60, 70 and 29 were resistant to INH, RMP, STR and EMB, respectively; 132 were resistant to at least one of the four anti-tuberculosis drugs and 51 were multi-drug resistant (MDR). Beijing genotype and retreated patients showed a significantly increased risk for developing MDR tuberculosis. Compared with the phenotypic data, the sensitivity and specificity for WGS to predict resistance were 96.7% and 98.6% for RMP, 75.5% and 97.1% for INH, 68.6% and 99.6% for STR, 93.1% and 93.7% for EMB, respectively. The most common mutations conferring RMP, INH, STR and EMB resistance were Ser450Leu (51.7%) in rpoB , Ser315Thr (44.3%) in katG , Lys43Arg (35.7%) in rpsL  and Met306Val (24.1%) in embB .
Conclusion: This study provides the first information on the prevalence and molecular characters of drug resistant M. tuberculosis  in the southern region of Xinjiang, China, which will be helpful for choosing early detection methods for drug resistance (ig, molecular methods) and subsequently initiation of proper therapy of tuberculosis in this area.
Keywords: Mycobacterium tuberculosis , whole-genome sequencing, resistance, prevalence, mutation, isoniazid, rifampicin, streptomycin, ethambutol