水莱茵海默氏菌 (Rheinheimera aquimaris) 淬灭细菌群体感应的机理研究

项目名称： 水莱茵海默氏菌 (Rheinheimera aquimaris) 淬灭细菌群体感应的机理研究

项目编号： No.41276135

项目类型： 面上项目

立项/批准年度： 2013

项目学科： 天文学、地球科学

项目作者： 朱虎

作者单位： 中国石油大学（华东）

项目金额： 85万元

中文摘要： 群体感应 (Quorum sensing, QS) 机制对细菌的生存与致病性至关重要，已成为研制新型抗菌药物的重要靶标。海洋微生物在生长过程中产生多种具有特殊生理功能的活性物质，这是开发药物先导化合物的珍贵原料宝库。本课题组已利用细菌QS系统作靶标，从青岛海域筛选出多株能淬灭QS系统的细菌。本研究拟以具有强烈QS淬灭活性的水莱茵海默氏菌为材料，利用紫色杆菌QS系统模型及HPLC-DAD-MS色谱技术平台，分析并鉴定其中能淬灭QS系统的活性作用因子及分子结构，研究其构效关系；同时利用生物物理技术和蛋白质工程手段，分析淬灭因子与QS系统受体蛋白的各种结合常数（淬灭速率常数、结合常数和结合位点数）及小分子-蛋白复合物的空间构像，解析其作用机制，进而阐明水莱茵海默氏菌淬灭QS系统的分子机理。本项目将为设计合成QS抑制剂、研发新型抗菌药物提供理论依据，并为海洋生物资源的深度开发及利用奠定坚实基础。

中文关键词： 水莱茵海默氏菌；群体感应；环色氨酸-丝氨酸；分子模拟；作用机制

英文摘要： Quorum sensing (QS) is a key regulator of survival and pathogenicity in bacterial species. It has therefore attracted significant research attention in recent years, offering promising anti-pathogenic drug targets. Marine microorganisms can, with their special life histories, produce bioactive substances during growth and metabolism. These bioactive compounds have special chemical structures and physiological functions. Therefore, they constitute a raw material library for screening drug lead compounds. Many marine bacteria have been screened from marine mud of the sea floor in the Qingdao Sea Area by the research group using QS system as a target. The metabolites of these strains can inhibit QS-regulated behaviors to a remarkable extent. This proposal will use R. aquimaris, which shows conspicuous QS-quenching activity, as the primary research material and study its growth characteristics and metabolic rules. In parallel, using QS system in Chromobacterium violaceum as a model in combination with HPLC-DAD-MS chromatography technology, the active factors that can quench QS in the secreted bioactive substance of R. aquimaris will be analyzed, their molecular structures will be detected, and the structure-activity relationship will be confirmed. The mode of the active factors and receptor protein in QS system inte

英文关键词： R. aquimaris；quorum sensing；cyclo(Trp-Ser)；molecular simulation；mode of action