Pseudomonas Aeruginosa Quorum Sensing Regulator Inhibitor Detection Screening System

Pseudomonas aeruginosa is an opportunistic pathogen. It can cause seriously acute and chronic infections in human beings, and is the third leading pathogen in nosocomial infections. Although some antibiotics are effective against P.aeruginosa, it bears innate resistance to many of the clinical important drugs. There is an urgent need to explore new antibacterial targets and develop novel antimicrobials to combat these drug resistant bacteria.Quorum-sensing (QS) system which is a recently discovered, global regulatory system is a cell-cell communication system. QS plays an important role in virulence and drug-resistance of P.aeruginosa, therefore QS represents a novel and promising target for controlling bacterial pathogenesis.In this study we constructed a luxCDABE-based reporter system that is suitable for high throughput screening for QS inhibitors. The system employs the promoters of P. aeruginosa lasI, and rhlA as the QS responsive reporters. It was used to screen for QS inhibitors from a small sets of natural compounds prepared from Chinese herbs, and a flavonoid compound DiphyllosideA, isolated from Epimidium wushanense T.S.Ying, was found to be active against Pseudomonas las QS system while exhibiting no effect on bacterial growth.