一组泛耐药鲍曼不动杆菌中发现拓普异构酶Ⅳ编码基因新的变异型

摘要

目的 调查一组泛耐药鲍曼不动杆菌中喹诺酮类耐药相关基因的存在与变化状况.方法 收集南通大学附属医院2011年1月-2011年4月患者标本中分离的泛耐药鲍曼不动杆菌共20株,采用聚合酶链反应(PCR)及序列分析的方法分析喹诺酮类药物作用靶位基因gyrA与parC,以及可移动遗传元件可介导的喹诺酮类耐药基因[ qnrA、qnrB、qnrS、qepA、aac( 6')-Ⅰ b-cr].结果 本组20株鲍曼不动杆菌均检出gyrA基因第83位密码子TCA→TTA有义突变(氨基酸序列Ser→Leu).parC基因第80位密码子TCG→TTG有义突变(氨基酸序列Ser→Leu),并同时存在3个同义突变(第40位密码子CCC→CCT同义突变;第41位密码子GTA→GTT同义突变;第44位密码子CGT→CGC 同义突变),且本组parC基因序列为新的变异型.可移动遗传元件可介导的喹诺酮类耐药基因qnrA、qnrB、qnrS、qepA、aac(6’)-Ⅰ b-cr均没有检出.结论 本组鲍曼不动杆菌耐喹诺酮类药物可认为主要与喹诺酮耐药决定区(QRDR)突变相关,发现parC基因新的变异型国内未见报道.%Objective To investigate the existence and variance of quinolone-resistance genes in a group of pan-drug resistant of Acinetobacter baumannii ( A.baumannii ).Methods Twenty strains of pandrug resistant A.baumannii were isolated from patients registered in Affiliated Hospital of Nantong University from January 2011 to April 2011.Drug target genes to quinolone (gyrA,parC) and quinolone-resistance genes mediated by mobile genetic elements [ qnrA,qnrB,qnrS,aac(6')-Ⅰ b-cr,qepA] were analyzed by PCR and verified by DNA sequencing.Results In all 20 strains of A.baumannii,the sense mutation was found in the quinolone resistance-determining region of the gyrA gene in the form of TCA to TTA at codon 83 (Ser-83-Leu).Moreover,in the quinolone resistance-determining region of the parC gene sense mutation was found in the form of TCG to TTG at codon 80 (Ser-80-Leu) and 3 synonymous mutations were CCC to CCT at codon 40,GTA to GT]T at codon 41 and CGT to CGC at codon 44.And parC gene was a new mutation.However,mutations were not found in quinolone-resistance genes mediated by mobile genetic elements [ qnrA,qnrB,qnrS,aac( 6 ' )-Ⅰ b-cr,qepA ].Conclusion Quinolone-resistance-determining region play a key role in resistance to quinolones in this group of A.baumannii.To our knowledge,this is first report about the emergence of the new mutation of parC gene in China.