Screening Of Inhibitor Of Pseudomonas Aeruginosa Population And Its Mechanism

Quorum sensing (QS) has been recognized as a widespread phenomenon in microorganisms and plays an important role in many pathogenic bacteria. It has been a novel target for the treatment of infectious diseases. In this report, we used biosensor strains Agrobacterium tumefaciens NT1to rapidly screen for the quorum sensing inhibitors(QSIs) from bacteria. There were about121putative positive strains screened from5389isolates that were obtained from soil of land and beach in the initial screening. A confirmatory bioassay was carried out after concentrating the putative positive culture supernatant and28strains remained to have QSI activity. Finally, we determined the strain A2, which could significantly inhibit biofilm formation of Pseudomonas aeruginosa PAO1, was belonged to the genus Pseudomonas by analysis of16S rDNA.We also discovered a new QSI, N-decanoyl-L-homoserine benzyl ester (C2), from38structural analogs of N-acylated-L_homoserine lactone (AHL). Virulence assays showed that C2down-regulated virulence factors(elastase, total protease and rhamnolipid) that are controlled by QS in P.aeruginosa without affecting growth. C2also inhibited the swarming motility of PAO1. Data from cDNA microarray and real-time RT-PCR suggested that C2activated gene qscR which encodes the QscR(quorum sensing control repressor) significantly(4.40fold determined in the cDNA microarray analysis and3.52fold determined in the real-time RT-PCR, respectly). We speculate that inhibition of virulence by C2may be in an indirectly manner that repressing las and rhl systems by activating QscR.