46株宋内志贺菌的基因突变与氟喹诺酮类药物耐药性的研究

摘要

目的：检测宋内志贺菌对喹诺酮类抗生素的耐药情况，探讨染色体介导DNA旋转酶和拓扑异构酶基因突变与志贺菌对喹诺酮类抗生素耐药的相关性。方法：用琼脂稀释法对46株宋内志贺菌进行耐药表型检测；PCR法检测喹诺酮耐药决定区相关基因gyrA、gyrB、gyrC、gyrE,并对产物进行序列分析；分析gyrA、gyrB、gyrC基因突变与喹诺酮类药物耐药的关系。结果：46株志贺菌对萘啶酸、环丙沙星、诺氟沙星、左氧氟沙星耐药率为：76.0%、30.4%、37.0%、17.3%；测序结果显示gyrA、gyrB、gyrC、gyrE的突变率为：90.0%、37.5%、65.0%、20.0%。结论：宋内志贺菌的gyrA基因突变是喹诺酮类药物耐药的主要机制，gyrA和gyrC的基因突变有协同作用，是引起细菌对氟喹诺酮类药物高水平耐药的重要因素。%Objective:To investigate the prevalence of quinolone resistance in Shigella strains, and its relation to DNA mutations of gyrase and topoisomerase genes.Methods:Antimicrobial susceptibility tests were performed in 46 Shigella strains by an agar diffusion method. The quinolone resistance determining region of gyrA, gyrB, gyrC, and gyrE genes were detected by polymerase chain reaction(PCR) .We evaluated the correlation between quinolone resistance and the changes of gyrA, gyrB, and gyrC genes statistically.Results: 76.0%、30.4%、37.0%、17.3% of tested Shigella strains had NAL、NOR、CIP and LVX drug-resistance, respectively.46 strains were randomly chosen for gene sequencing and genetic mutation rates of gyrA、gyrB、gyrC、gyrE were 90.0%、37.5%、65.0% and 20.0%.Conclusions:Genetic mutation of gyrA is the main mechanism of drug resistance to quinolone.The cooperative effect of gyrA and gyrC is the key factor which cause the drug resistance of bacteria to quinolone.