Molecular Characteristics and Drug Resistance of Mycobacterium tuberculosis Isolate Circulating in Shaanxi Province, Northwestern China

Objective: Shaanxi is the most highly populated province with high burdens of tuberculosis in northwestern China. The aim of this study was to investigate the molecular characteristics and drug resistance of Mycobacterium tuberculosis isolates from Shaanxi province of China in 2018. Methods: Phenotypic drug susceptibility testing and spoligotyping methods were performed on 518 M. tuberculosis isolates; drug-resistant isolates were sequenced in 11 drug loci, including katG, inhA, oxyR-ahpC, rpoB, embB, rpsL, rrs(1) (nucleotides 388-1084), gyrA, gyrB, rrs(2) (nucleotides 1158-1674), and eis. Results: The prevalences of isoniazid, rifampicin, ethambutol, streptomycin, ofloxacin, and kanamycin resistance were 22.0%, 19.3%, 7.9%, 23.8%, 10.4%, and 3.3%, respectively. The Beijing family (82.8%) was the predominant genotype, followed by the T (9.3%), H (0.6%), CAS (0.4%), LAM (0.4%), and U (0.4%) families. The percentage of Beijing genotype in a central area (88.1%) was higher than in the south (77.3%) and the north area (80.1%) (p < 0.05), while the sex, age, and treatment history between Beijing and non-Beijing family were not statistically different. Mutation analysis found that the most prevalent mutations were katG315, rpoB531, embB306, rpsL43, gyrA94, and rrs1401; the Beijing family exhibited a high rate of isoniazid-resistant isolates carrying katG315 mutations (p < 0.05). Furthermore, compared with the phenotypic data, the sensitivities of isoniazid, rifampicin, ethambutol, streptomycin, ofloxacin, and kanamycin resistance by sequencing base on 11 loci were 85.1%, 94.0%, 53.7%, 74.8%, 77.8%, and 64.7%, respectively. Conclusions: Shaanxi has a serious epidemic of drug-resistant tuberculosis, Beijing family is the predominant genotype, and the distribution showed geographic diversity. The prevalence of Beijing genotypes has a tendency to promote the transmission of high-level isoniazid-resistant M. tuberculosis. Besides, the hot spot regions localized in the embB, rrs(2), and eis gene appear not to serve as excellent biomarkers for predicting ethambutol and kanamycin resistance in Shaanxi.