抗生素诱导鲍曼不动杆菌多重耐药AdeABC外排泵中核糖开关研究

项目名称： 抗生素诱导鲍曼不动杆菌多重耐药AdeABC外排泵中核糖开关研究

项目编号： No.81373454

项目类型： 面上项目

立项/批准年度： 2014

项目学科： 医药、卫生

项目作者： 凌保东

作者单位： 成都医学院

项目金额： 65万元

中文摘要： 由AdeRS调节的AdeABC外排泵在介导鲍曼不动杆菌多重耐药中发挥重要作用。本课题组成员研究证实核糖开关调控氨基糖甙类抗生素耐药基因表达，我们前期研究显示抗生素诱导AdeABC中adeC高表达，而adeB和adeC基因间存在核糖开关相关非翻译区及类似核糖开关的发夹结构，因此我们提出多重耐药鲍曼不动杆菌中adeC核糖开关调控AdeABC外排泵基因表达的假说。本课题拟通过载体构建、细菌体内功能实验，核糖开关与抗生素体外相互作用等方法，确定adeC核糖开关构象变化模型，明晰adeC核糖开关及寻找抗生素和adeC核糖开关结合位点。通过阐明adeC核糖开关调控AdeABC外排泵或AdeRS表达，揭示核糖开关在多重耐药外排泵机制中的作用，为发现新的药物作用靶点，研制新的抗菌药物及指定新的治疗策略奠定基础。

中文关键词： 鲍曼不动杆菌;AdeABC;核糖开关;诱导耐药;

英文摘要： The AdeABC efflux pump, which is regulated by the AdeRS two-component system, plays important role in multidrug-resistant (MDR) A.baumannii. Our recent work showed that the expression of adeC in A.baumannii was increased at the level of transcription after antibiotic induction. There was a similar riboswitch structure of hairpin between adeB and adeC. Based on our preliminary data and our recent publication of an aminoglycoside-binding riboswitch, we propose that adeC riboswitch can regulate the efflux pump genes in MDR A.baumannii.We will construct adeC riboswitch structural model and locate the antibiotic binding site by 1) the construction of the reporter gene expression system to verify the riboswitch function in bacteria, and 2) the interaction between the riboswitch and antibiotics. Based on our experimental data and the use of bioinformatic tools, the research in this application will lead to the identification of adeC riboswitch controling the expression of the AdeABC efflux pump genes or AdeRS. The overall objective is to understand the mechanism of inducible antibiotic resistance for developing new antibiotic targets and it will contribute to developing novel treatments for the infection diseases caused by MDR Acinetobacter baumannii.

英文关键词： Acinetobacter baumannii;AdeABC;Riboswitch;Induce resistance