以耐药细菌菌群传感系统为靶点的新抗菌药物研究已成为抗感染药物研发的热点。本课题组前期研究发现鱼腥草素钠（SH）可有效抑制铜绿假单胞菌生物被膜形成，并显著抑制菌群传感系统信号分子产生和Las系统关键调控基因lasR的表达及其控制的相关基因表达。因此，本课题提出以下假说：SH与LasR蛋白结合长链信号分子结构类似，通过竞争性结合LasR蛋白，抑制Las菌群传感系统，从而抑制该菌的生物被膜发育和毒力因子产生。基于以上基础，本课题拟分析SH对于该菌的转录组、长链信号分子合成的影响，检测SH和长链信号分子与LasR蛋白的竞争性结合能力，并分析SH对于由Las系统调控的相关因子的影响。另一方面，本课题拟分析SH对于流动模型下膜分散过程的影响，并检测生物膜显微结构的变化，进一步检测相关基因和产物受SH的影响。本课题研究将阐明SH抑制菌群传感系统的分子机制，并为SH的结构改造和新的临床应用提供理论基础。

New antimicrobial agents targeting quorum sensing system of drug resistant bacteria has been focused in research and development of antimicrobial drugs. Based our previous research, we discovered that sodium hottufonate(SH) effectively inhibits the biofilm formation, and AHL signal molecule biosynthese of quorum sensing system and key regulatory gene lasR and controled genes of P. aeruginosa. Thus, we propose a hypothesis that SH competively binds LasR to inhibit Las quorum sensing system to inhibit biofilm development and production of virulence factors due to the simlar structure of SH and long chain signal molecular binding LasR. Based on the above basis, this project plans to analyze the effects of SH on transcriptome and biosynthesis of long chain AHL molecule, and determine competively binding activity of SH and LasR aginst long chain AHL molecule, and discover the effects of SH on the factors regulated by Las system. Hence, we plan to analyze the effects of SH on the biofilm dispersion in flow biofilm model, and detect the changs of biofilm microstructure under SH treatment, and determine the effects of SH on the biofilm dispersion related genes and metabolites. Therefore, the progress of the project would shed light on the mechanism of SH inhibit effects on QS system of P. aeruginosa, and provide the basis of modification of chemcial structure and possible clincal application of SH as a new QS inhibiting antimicrobial agent.