携带氨基糖苷类耐药基因aacC2的质粒pA1137耐药机制研究  

Antibiotic-resistant mechanisms of plasmid pA1137 carrying aminoglycoside resistance gene aacC2

作　　者：占喆 冯娇 殷喆 赵禹宗 蒋晓圆 罗文博 曾利军 沈杨 高波[2] 周冬生[1,2] ZHAN Zhe;FENG Jiao;YIN Zhe;ZHAO Yu-zong;JIANG Xiao-yuan;LUO Wen-bo;ZENG Li-jun;SHEN Yang;GAO Bo;ZHOU Dong-sheng(Anhui Medical University, Hefei 230032, China;State Key Laboratory of Pathogen and Biosecurity, Institute of Microbiology and Epidemiology, Academy of Military Medical Sciences, Academy of Military Sciences, Beijing 100071, China)

机构地区：[1]安徽医科大学,合肥230032 [2]军事科学院军事医学研究院微生物流行病研究所病原微生物生物安全国家重点实验室,北京100071

出　　处：《军事医学》2017年第12期973-977,共5页Military Medical Sciences

基　　金：国家重点研发计划资助项目(2016YFC1200100)

摘　　要：目的对携带氨基糖苷类耐药基因aacC2的阴沟肠杆菌质粒pA1137全序进行分析并研究其耐药机制。方法 PCR实验检测相关菌株耐药基因,接合转移实验验证质粒pA1137是否具备可转移特性,抗生素敏感实验检测相关菌株耐药谱,采用全基因组测序分析质粒基因环境、移动元件,并研究其耐药机制。结果阴沟肠杆菌A1137同时携带碳青霉烯酶耐药基因blaIMP-8和氨基糖苷类耐药基因aacC2和aacA4。blaIMP-8和aac A4基因均位于染色体上,而aacC2基因则位于pA1137质粒上。pA1137是大小为68.97 kb的IncFⅡ型质粒,GenBank登录号为MF190369。该质粒含有典型的多复制子结构且有完整的接合转移区,可通过接合转移方式进入受体菌EC600并表达相应的耐药谱。结论 IncFⅡ型质粒pA1137有一个外源插入区,是首次发现基于Tn5403转座子的aacC2-tmrB相关耐药区,可稳定遗传并介导阴沟肠杆菌A1137对氨基糖苷类抗生素耐药。Objective To achieve detailed genomic characterization and investigate the antibiotic-resistant mechanisms of plasmid pAl 137 carrying the aminoglycoside resistance gene aacC2. Methods Antibiotic-resistant genes were determined by PCR. Conjugation experiments were performed to verify the transferability of plasmid pA1137. The minimum inhibitory concentration （ MIC ） values of bacterial strains were tested with microdilution method. The genetic background, mobile elements and antibiotic resistance mechanisms of pal 137 were determined using a whole genome sequencing method. Results Both carhapenem-resistant gene blaIMP-8 and aminoglycoside-resistant genes aacC2 and aacA4 were carried by A1137 isolated from Enterobacter cloacae （ECL）. aacC2 was located in plasmid pal 137 while the other two resistant genes were observed in chromosomes. Plasmid pA1137 was an IncF Ⅱ plasmid, whose total length was 68.97 kb, and GenBank accession number was MF190369. Plasmid pA1 137 contained multiple replieons and intact conjugative transfer regions, so it could he transferred into ECL through conjugation experiments and confer corresponding antibiotic resistance to the transconjugant A1137-EC600, Conclusion IncF Ⅱ plasmid pa1137 has a single accessory region, the first reported Tn5403-based aacC2-tmrB-related region, which can cause stable inheritance and mediate the resistance to aminoglycoside antibiotics in ECL A1137.

关 键 词：阴沟肠杆菌 pA1137 aacC2 

分 类 号：R446.5[医药卫生—诊断学]