志贺菌敏感株诱导耐药与marOR基因突变关系

Correlation between drug-resistance of sensitive strain of Shigella flexneri and mutation of marOR gene

目的对志贺菌敏感株进行诱导使其耐多药,研究其诱导耐药前后marOR基因的差异。方法用4类抗生素的次抑菌浓度对临床分离鉴定的志贺菌敏感株进行诱导耐多药试验。对志贺菌敏感株及诱导耐多药株的marOR基因进行聚合酶链反应(PCR)扩增后,测序比较其诱导耐药前后marOR基因序列的差异。结果成功获得志贺菌诱导耐多药株,命名为YD株;其最小抑菌浓度(MIC)分别为初始菌株的6～8倍;该诱导耐药株对庆大霉素、诺氟沙星、磺胺甲基异恶唑、头孢噻吩等均耐药;测序结果发现诱导耐药株marOR基因YD株有6个位点出现突变,其中5个为同义突变,1个为错义突变(1630位点A→G,赖氨酸→精氨酸)。结论 marOR基因的突变可能是志贺菌诱导耐药的调控机制之一。

Objective To induce multidrug resistance of the sensitive strain of Shigella flexneri and to study the multi-drug resistance regulating gene mutations.Methods Clinical sensitive Shigella flexneri strain was induced into anti-drug strain by 1/2 minimum inhibitive concentration（MIC） induced trails of four antibiotics.MarOR gene in sensitive and induced anti-multidrug strain was amplified with polymerase chain reaction（PCR）.The PCR products were sequenced and compared.Results Induced anti-multidrug strain of Shigella flexneri was obtained successfully.The strain was resistant to gentamycin（GF）,norfloxacin（NOR）,cotrimoxazole（SMZ）,and cefalotin（CF）.DNA sequence analyses of marOR in sensitive and induced anti-multidrug strain revealed seven point mutations.Conclusion The marOR gene mutations may play an important role in the regulation of multi-drug resistance in Shigella spp.