鲍曼不动杆菌对氨基糖苷类药物耐药机制研究

目的研究对氨基糖苷类抗菌药物耐药的鲍曼不动杆菌分子流行病学特征和耐药机制。方法采用琼脂稀释法检测抗菌药物对鲍曼不动杆菌的最低抑菌浓度(MIC),采用肠杆菌科基因间重复一致性序列(ERIC)-聚合酶链反应(PCR)研究耐药菌株的分子流行病学特征,采用特异性PCR、序列分析和接合试验研究介导耐药的分子机制。结果临床分离菌株对包括氨基糖苷类抗菌药物在内的多种药物广泛耐药,同源性分析显示属于7个流行克隆型。所有分离菌株均扩增出介导氨基糖苷类抗菌药物耐药的修饰酶和药物"外排泵"基因,部分菌株扩增出甲基化酶基因。结论修饰酶和甲基化酶介导鲍曼不动杆菌临床分离株对氨基糖苷类药物耐药,药物"外排泵"参与介导耐药机制形成,垂直传播和通过耐药性质粒的水平传递可能是耐药菌株播散的主要方式。

Study on the molecular mechanism of aminoglycoside resistance to Acinetobacter Baumannii

Objective To investigate the molecular epidemiology and mechanism of aminoglycoside resistance to Acinetobacter baumannii isolates.Methods Agar-dilution was carried out to detect the minimum inhibitory concentration（MIC）,and enterobacterial repetitive intergenic consensus（ERIC）-polymerase chain reaction（PCR） was performed to analyze the molecular epidemiology of aminoglycoside-resistance isolates.Specific PCR,DNA sequencing,conjugation experiments were carried to confirm the transmission mechanism.Results All the clinical isolates were resistant to most drugs including aminoglycosides,and ERIC-PCR showed the isolates belonged to 7 genotypes.Specific PCR and DNA sequencing revealed that all isolates encoded aminoglycoside-modifying enzyme genes,efflux pump gene and methylase gene.Conclusions Producing of aminoglycoside-modifying enzyme and methylase mainly contribute to reduce the susceptibility of aminoglycosides in Acinetobacter baumannii.Efflux pump overexpression may as a cofactor in high-level aminoglycoside resistance.Vertical transmission and plasmid-mediated horizontal transmission are probably the principal epidemical mechanisms.