耐多药结核分枝杆菌耐药相关基因突变特征分析

目的了解中国耐多药结核分枝杆菌耐药相关基因的分子特征。方法对138株耐多药结核分枝杆菌和45株敏感菌的耐药相关基因inhA、katG和oxyR-ahpC间隔区(异烟肼)、rpob(利福平)、gyrA(氧氟沙星)和rrs(卡那霉素)进行序列测定,分析其基因突变特点。结果 138株耐多药结核分枝杆菌中,14.4%的菌株inhA基因发生突变,72.5%菌株的katG基因发生突变,15.9%菌株的oxyR-ahpC基因发生突变,同时考虑这3种基因,异烟肼耐药相关基因突变检出率可达90.6%;94.2%菌株的rpoB基因发生突变,74.5%菌株的gyrA基因发生突变,61.1%菌株的rrs基因发生突变,主要的突变位点为katG315(66.7%),inhA-15(9.4%),oxyR-ahpC-10(5.1%),rpoB516(13.8%),526(26.1%)和531(49.3%),gyrA90(21.6%)和94(51%),rrs1401(61.1%)。结论我国耐多药结核菌异烟肼、利福平、氧氟沙星和卡那霉素耐药相关基因最常见突变为katG315、inhA-15,rpoB531、526和516,gyrA94和90,rrs1401。

Characteristics of drug resistance associated mutations in multi-drug resistant Mycobacterium tuberculosis

Objective To analyze the molecular characteristics of drug-resistance associated genes of multi-drug resistant Mycobacteriurn tuberculosis （MDR-TB）. Methods Drug-resistant associated genes of inhA, katG, oxyR-ahpC （ isoniazid）, rpoB （ rifampicin）, gyrA （ofloxacin） and rrs （kanamycin） of 138 MDR-TB strains and 45 sensitive strains isolated in China were detected. Results Among 138 MDR-TB strains, 14.4% had mutations in inhA, 72. 5% had mutations in katG, and 15.9% had mutations in oxyR-ahpC. The detection rate of the drug resistant mutations to isoniazid of the 3 gens mentioned above was 90. 6%. 94. 2% had rpoB mutation, 74. 5% had gyrA mutation, and 61.1% had rrs mutation. The majority of mutations were at katG315 （66. 7% ）, inhA - 15 （9.4%）, oxyR-ahpC - 10 （5. 1%）, rpoB516 （13.8%）, 526 （26. 1%）, 531（49.3%）, gyrA90 （21.6%）, 94 （51%） andrrs1401 （61.1%）. Conclusion The most common gene mutations associated with isoniazid, rifampicin, ofloxacin and kanamycin resistance in MDR-TB strains in China were at katG315, inhA - 15, rpoBS16, 526, 531, gyrA90, 94 and rrs1401, respectively.