绿脓杆菌新型集成群体感应系统的功能及机理研究

项目名称： 绿脓杆菌新型集成群体感应系统的功能及机理研究

项目编号： No.31330002

项目类型： 重点项目

立项/批准年度： 2014

项目学科： 生物科学

项目作者： 张炼辉

作者单位： 华南农业大学

项目金额： 291万元

中文摘要： 群体感应是微生物中广泛保守存在的一种细胞与细胞间的通信机制，协调细菌各种群体活动，研究群体感应机制对控制和预防细菌感染至关重要。绿脓杆菌采用由las、pqs及rhl调控系统组成的群体感应网络协调其毒力基因表达。但不少临床分离株均发现中央Las系统功能突变受损，促使我们探索绿脓杆菌是否存在一种可能取代las的机制，并最近分离鉴定到一种新群体感应信号IQS。阻断 IQS合成导致pqs及rhl系统的群体感应并显著降低菌株毒力。IQS产生受las严格控制但同时也被磷酸贫乏状况激活，磷酸贫乏是细菌感染过程中的常见胁迫信号。我们的研究结果首次证明绿脓杆菌存在一种新型集成群体感应系统，上连中央las系统和磷酸胁迫应激反应机制，下接pqs及rhl系统。本项目旨在研究IQS受体蛋白和下游调控因子，分析IQS合成途径和分子运输机理，明确IQS信号通路和调节机制，为阐明绿脓杆菌群体感应机理和致病调控机制奠定基础

中文关键词： 群体感应;新型;功能;致病调控;

英文摘要： Quorum sensing (QS) is a widely conserved cell-to-cell communication mechanism which coordinates various bacterial community activities including virulence gene expression and biofilm formation. It is of vital importance to study bacterial quorum sensing mechanisms for design and developing new strategies to control and prevent bacterial infections. Pseudomonas aeruginosa employs a hierarchical quorum sensing (QS) network consisting of las, pqs and rhl regulatory elements to coordinate expression of bacterial virulence genes. However, clinical isolates frequently contain loss-of-function mutations in the central las system. This motivated us to search for a mechanism that may functionally substitute las, which led to identification of a novel QS signal IQS. Disruption of IQS biosynthesis paralyses the pqs and rhl QS systems and attenuates bacterial virulence. Production of IQS is tightly controlled by las under normal culture conditions but is also activated by phosphate limitation, a common stress bacteria encountered during infections. Our findings unveiled a novel integrated QS system which connects the central las system and phosphate-stress response mechanism to the down-stream pqs and rhl regulatory systems. In this project, we aim to investigate the signaling pathway and regulatory mechanisms of IQS. We will determine the IQS receptor protein and down-stream regulators. In addition, we will also analyze the synthetic pathway and transportation mechanism of IQS.

英文关键词： Quorum sensing;novel;function;pathogenesis regulation