群体感应（QS）是新型抗耐药菌药物研发的重要靶标，pqs系统在QS调控网络中起到关键纽带作用。本项目基于pqs系统的PqsR受体蛋白及PQS信号分子对前期构建的抗菌活性小分子数据库进行了虚拟筛选，并通过提取物的生物膜抑制活性实验，确定了莲子心较强的QS抑制活性。本项目拟在前期研究基础上，进一步分离、鉴定莲子心化学成分；通过生物膜抑制实验及绿脓菌素、鼠李糖脂和弹性蛋白酶等毒力因子的释放抑制实验，评价单体化合物活性；采用PQS信号分子检测模型、大肠杆菌异源表达的pqs系统以及铜绿假单胞菌QS系统基因表达调控，研究活性化物对pqs系统的调控作用机制；利用活性化合物与PqsR受体对接，进一步验证和解释其作用机制；应用3D-QSAR模块，研究化合物构效关系，寻找先导化合物。本项目将从天然产物中更高效发现QS抑制活性化合物，为抗耐药菌药物的研发奠定基础。

Quorum sensing (QS) system has been a promising target for developing novel antibacterial agents. The pqs system plays an important role in quorum sensing regulatory network. The potent QS inhibitory activity of Plumula nelumbinis was confirmed by the biofilm inhibition of its extractions, and also by virtual screening for 20000 reported antibacterial chemical constituents based on the PqsR receptor and PQS signal molecule. On the basis of previous work, the project aims to discover the active compounds of Plumula nelumbinis and study the mechanism on pqs system: separation and identification of the chemical constituents of Plumula nelumbinis; evaluation of biofilm, pyocyanin, rhamnolipid and elastase inhibitory activity of the compounds; mechanisms of the active compunds on pqs system by the inhibition of the PQS signal molecule, heterologous expression of pqs system in E.coli, and gene expression of QS regulatory system of Pseudomonas aeruginosa; further verification and explanation of the molecular mechanisms by docking with the PqsR receptor; structural optimization to looking for lead compounds based on 3D-QSAR. This project provoid a more efficient way to discover QS inhibitory of natural products from a new perspective, and play a solid foundation for further antibacterial drug design and development.