Genotypicdiversity of drug-resistant Mycobacterium tuberculosis isolates from Hebei, China

Drug-resistant tuberculosis (DR-TB), particularly multidrug-resistant tuberculosis (MDR-TB), has been identified as a major challenge for effective TB control. For rapid detection and proper treatment, molecular assays based on the identification of mutations in genes associated with drug resistance have been established to determine drug resistance. However, there is as yet little information about drug resistance-associated mutations of clinical Mycobacterium tuberculosis isolates from Hebei. In this study, four genetic loci katG, inhA, oxyR-ahpC intergenic region and rpoB were sequenced among 276 DR-TB isolates from Hebei to understand the association between specific mutations, drug resistance phenotypes and spoligotyping genotypes. Altogether, 83.8% of INH resistant isolates harbored at least one mutation of katG, inhA, and oxyR-ahpC intergenic region and 78.4% of RIF resistant isolates harbored one or more mutations in rpoB. The predominant mutation patterns of rpoB and katG in Hebei was Ser531Leu and Ser315Thr, respectively. Additionally, 91.2% of MDR isolates harbored at least one mutation in these four targeted fragments. Compared with the phenotypic data, the sensitivity and specificity of co-testing of katG, inhA promoter and oxyR-ahpC intergenic region for INH resistance were 83.8% and 96.8%, respectively and the rpoB exhibited a sensitivity of 78.4% and a specificity of 95.3% for RIF resistance. Furthermore, there was no association between drug resistance-conferring mutations and spoligotypes. This finding will be useful for the establishment of rapid molecular diagnostic methods in Hebei province, China.