外排系统在鲍曼不动杆菌三氯生（消毒剂）耐受中的作用机制

项目名称： 外排系统在鲍曼不动杆菌三氯生（消毒剂）耐受中的作用机制

项目编号： No.81201327

项目类型： 青年科学基金项目

立项/批准年度： 2013

项目学科： 医学四处

项目作者： 皮博睿

作者单位： 浙江大学

项目金额： 23万元

中文摘要： 鲍曼不动杆菌以克隆播散方式在我国医院内广泛流行，消毒隔离是控制其克隆播散的重要措施，消毒剂耐受易导致消毒失败，医院感染暴发。三氯生是在日用品中广泛添加的消毒剂，低浓度的三氯生易引起细菌产生耐受性，并能诱导抗菌药物出现交叉耐药，因此急需阐明鲍曼不动杆菌对三氯生耐受的作用机制。研究发现外排系统在细菌对消毒剂耐受以及消毒剂与抗菌药物交叉耐药中极可能发挥重要作用，申请人前期研究筛选到20株对三氯生不同水平耐受的鲍曼不动杆菌，已从表型上证实了外排系统是引起三氯生耐受的重要机制。已完成的全基因组测序显示鲍曼不动杆菌染色体上有大量功能未知的外排相关基因，它们与三氯生耐受的关系尚不明确，如用传统技术逐一进行研究周期长、耗费大。因此，本项目拟通过转录组测序，系统鉴定出鲍曼不动杆菌中介导三氯生耐受的外排系统，阐明其作用机制，同时明确能够与三氯生产生交叉耐药的抗菌药物，揭示三氯生对抗菌药物耐药性的影响。

中文关键词： 三氯生；多重耐药；活性氧；RNA-seq；FabI

英文摘要： Acinetobacter baumannii (A. baumannii) spread widely in China. Disinfection and isolation are crucial for control the epidemiology of A. baumannii. Resistance to biocides will lead to failure of disinfection and cause the outbreak of nosocomial infections. Triclosan is a biocide used in many product categories, low concentration of which will trigger the expression of resistance and cross-resistance in bacteria. Efflux of antimicrobials may play an important role on the resistance to biocides and antibiotics. Twenty A. baumannii isolates with reduced susceptibility to triclosan have already been chosen. Efflux inhibition test has been performed to demonstrate active efflux is one of the mechanisms of triclosan resistance. A number of other putative drug transporters have been identified by whole-genome sequencing of A. baumannii strains ZJ06, of which the effects on the resistance to triclosan remain to be verified. Considering the high cost of traditional technology, the transcriptome of A. baumannii will be determined by use of high-throughput sequencing to identify the efflux pumps which could extrude triclosan and to elucidate the effects of active efflux on triclosan resistance. The association between triclosan resistance and resistance to antibiotics will also be demonstrated in this project.

英文关键词： triclosan；multidrug resistance；reactive oxygen species；RNA-seq；FabI