Zhao Li-Li, Chen Yan, Liu Hai-Can, Xia Qiang, Wu Xiao-Cui, Sun Qing, Zhao Xiu-Qin, Li Gui-Lian, Liu Zhi-Guang, Wan Kang-Lin
National Institute for Communicable Disease Control and Prevention, Chinese Center for Disease Control and Prevention/State Key Laboratory for Infectious Disease Prevention and Control, Beijing, China.
Antimicrob Agents Chemother. 2014;58(4):1997-2005. doi: 10.1128/AAC.01792-13. Epub 2014 Jan 13.
To investigate the molecular characterization of multidrug-resistant tuberculosis (MDR-TB) isolates from China and the association of specific mutations conferring drug resistance with strains of different genotypes, we performed spoligotyping and sequenced nine loci (katG, inhA, the oxyR-ahpC intergenic region, rpoB, tlyA, eis, rrs, gyrA, and gyrB) for 128 MDR-TB isolates. Our results showed that 108 isolates (84.4%) were Beijing family strains, 64 (59.3%) of which were identified as modern Beijing strains. Compared with the phenotypic data, the sensitivity and specificity of DNA sequencing were 89.1% and 100.0%, respectively, for isoniazid (INH) resistance, 93.8% and 100.0% for rifampin (RIF) resistance, 60.0% and 99.4% for capreomycin (CAP) resistance, 84.6% and 99.4% for kanamycin (KAN) resistance, and 90.0% and 100.0% for ofloxacin (OFX) resistance. The most prevalent mutations among the MDR-TB isolates were katG315, inhA15, rpoB531, -526, and -516, rrs1401, eis-10, and gyrA94, -90, and -91. Furthermore, there was no association between specific resistance-conferring mutations and the strain genotype. These findings will be helpful for the establishment of rapid molecular diagnostic methods to be implemented in China.
为了研究中国耐多药结核病（MDR-TB）分离株的分子特征，以及赋予耐药性的特定突变与不同基因型菌株之间的关联，我们对128株MDR-TB分离株进行了间隔寡核苷酸分型（spoligotyping），并对9个位点（katG、inhA、oxyR-ahpC基因间隔区、rpoB、tlyA、eis、rrs、gyrA和gyrB）进行了测序。我们的结果显示，108株分离株（84.4%）为北京家族菌株，其中64株（59.3%）被鉴定为现代北京菌株。与表型数据相比，DNA测序对于异烟肼（INH）耐药性的敏感性和特异性分别为89.1%和100.0%，对于利福平（RIF）耐药性为93.8%和100.0%，对于卷曲霉素（CAP）耐药性为60.0%和99.4%，对于卡那霉素（KAN）耐药性为84.6%和99.4%，对于氧氟沙星（OFX）耐药性为90.0%和100.0%。MDR-TB分离株中最常见的突变是katG315、inhA15、rpoB531、-526和-516、rrs1401、eis-10以及gyrA94、-90和-91。此外，赋予耐药性的特定突变与菌株基因型之间没有关联。这些发现将有助于在中国建立快速分子诊断方法。
