耐多药结核分枝杆菌对喹诺酮类药物的耐药性与gyr基因突变的初步研究

摘要

目的 分析耐多药结核分枝杆菌(Multiple drug-resistant tuberculosis,MDR-TB)临床分离株的gyr基因突变特点,探讨MDR-TB对喹诺酮类药物耐药产生与gyr基因突变的关系.方法 采用比例法对耐多药结核临床分离菌株进行氧氟沙星的药物敏感性检测,应用DNA直接测序法检测MDR-TB的gyr基因突变情况.结果 125株MDR-TB临床分离株中,50株对喹诺酮类耐药,耐药率为40%.50株耐药菌株中,40株gyr基因发生突变:其中39株gyrA基因突变,突变率为78%,突变位点包括90,91和94位氨基酸;5株gyrB基因突变,其中4株合并gyrA基因突变,gyrB基因突变位点为500,506,534和539位氨基酸.结论 MDR-TB中的喹诺酮类药物耐药态势比较严峻,其对喹诺酮类药物耐药机制主要与gyrA基因突变有关.%In order ot analyze the characteristics of gyr gene mutations in clinical isolates from the patients with multidrug resistant tuberculosis (MDR-TB) and the relation between MDR-TB with quinolone resistance and gyr gene mutations,the susceptibility of the MDR-TB clinical isolates to quinolones was tested by the proportion method.Gyr gene mutations of MDR-TB strains were detected by direct DNA sequencing.The results showed that there were 50 strains with quinolone resistance in 125 MDR-TB clinical isolates.The quinolone resistance rate was 40％.There were 40 with gyr mutations in 50 MDRTB with quinolone resistance.Of 40 quinolone resistant MDR-TB with gyr mutations, 39 mutated at condon 90, 91 and 94 of gyrA gene with a mutation rate of 78％.For 5 gyrB mutatans, 4 were associated with gyrA gene mutations.The mutation sites of gyrB were at condon 500, 506, 534 and 539 of gyrB gene.This study shows that the situation of MDR-TB with quinolone resistance is very serious.The mechanism of quinolone resistance in MDR-TB is mainly in connection with the mutation of gyrA gene.