结核分枝杆菌喹诺酮类药物耐药与gyr基因突变的初步研究

Study on gyr mutation in quinolone-resistant Mycobacterium tuberculosis isolated from Fujian province

目的初步了解福建省结核分枝杆菌分离株喹诺酮类药物耐药性与gyr基因突变的关系。方法对来源于福建省结核病耐药性监测30个监测点纳入的75株耐多药结核分枝杆菌分离菌株,行包含gyrA、gyrB基因喹诺酮类药物耐药决定区(QRDR)序列测定,以结核分枝杆菌H37Rv标准株DNA序列为参比序列进行比较分析。结果 75株耐多药结核分枝杆菌中,56株氧氟沙星敏感株均未检测到gyrA基因发生突变,19株氧氟沙星耐药株检测到16株(84.21%,16/19)gyrA基因发生突变,其中9株突变发生在第91位密码子,4株发生在第94位密码子,3株发生在第95位密码子,发现Ser95Asn为新突变类型;所有菌株均未检测到gyrB基因发生突变。结论 gyrA基因突变是耐喹诺酮结核分枝杆菌耐药性的主要分子机制;gyrA基因的突变主要发生在第91位、94位、95位密码子上。

Objective To observe the gyr mutations in quinolone-resistanct Mycobacterium tuberculosis （M. tuberculosis） isolated in Fujian province. Methods 75 MDR M. tuberculosis strains isolated from 30 survey sites were collected and analyzed for gyr mutations by QRDR sequencing in gyrA and gyrB genes. Sequence alignment was conducted to pick up mutation in which the DNA sequence of H37Rv strain was used as a reference. Results Out of 75 MDR M. tuberculosis isolates, 56 were ofloxacin sensitive in which no gyrA mutations were identified. However, gyrA mutations were picked up in 16 out of 19 （84.21%） ofloxacin resistant strains, and the mutations were found in codons of 91 （9/16） , 94 （4/16） and 95 （3/16） . The Ser95Asn mutation was newly identified in Fujian. No gyrB mutation was found in this study. Conclusions GyrA mutation is the leading cause of M. tuberculosis resistance to quinolones which mainly happens in codon of 91, 94 and 95.