Study On The Inhibitory Effect Of Several Chinese Herbal Extract And Stilbenoids On Bacterial Quorum Sensing

For a long time, the widespread use of traditional antibiotics has led to the emergence of multi-drug-resistant pathogenic bacteria. Those multi-drug-resistant pathogenic bacteria have been a serious threat to human’s life and health. Recent studies have shown that bacteria use quorum sensing (QS) system to regulates a number of important physiological functions, such as the production of virulence factor and the formation of biofilm in pathogen. In this case, disturbing the quorum sensing system by appropriate quorum sensing inhibitors (QSIs) may be a promising alternative strategy to fight bacterial infections especially those caused by multidrug resistant bacterial strains. QSIs can reduce the pathogenicity of pathogens without killing them, and then reduce the use of antibiotics to avoid evolutionary pressure on bacterial population to develop resistance.In this study, we used Chromobacterium violaceum CV026 and Agrobacterium tumefaciens KYC55 as report strains to screen the quorum sensing inhibitory activity of the crude extracts from 10 common Chinese medicine herbs and the small molecule compounds that has been isolated and purified in our laboratory. We found that SJY-10 extract could interrupt A.tumefaciens KYC55 quorum sensing system, but had no effect on C.violaceum CV026, and the QSI activity of SJY-10 extract was superior to the garlic extract (positive control);while SJY-1 extract and resveratrol could inhibit C.violaceum CV026 quorum sensing system, but had no effect on A.tumefaciens KYC55, and resveratrol, belong to stilbenoids, had better QSI activity than garlic extract (positive control).Subsequently, quorum sensing inhibition activity of ten stilbenoids including resveratrol were tested using C.violaceum CV026 as the bio-indicator strain and the structure-activity relationship was also investigated. In addition to the stilbene monomer resveratrol, we report here, for the first time, that piceatannol and oxyresveratrol possess the QSI activity against C.violaceum CV026. Purple pigment extraction experiment further verified the quorum sensing inhibitory activity of resveratrol, piceatannol and oxyresveratrol:at the sub-MIC concentrations, these three compounds could significantly inhibit the production of purple pigment in a concentration dependent manner.Pseudomonas aeruginosa is one of the most common clinical opportunistic pathogens which can cause serious acquired infections. The production of its virulence factors is regulated by the quorum sensing system. We also studied the effects of resveratrol, piceatannol and oxyresveratrol on P.aeruginosa PAO1 quorum sensing system at sub-lethal concentrations. Our results showed that resveratrol, piceatannol and oxyresveratrol could significantly inhibit the production of pyocyanin and swarming in P. aeruginosa PAO1 without inhibiting their growth. Further transcriptome analyses showed that resveratrol, piceatannol and oxyresveratrol suppressed the expression of QS-induced genes:lasR, lasl, rhlR and rhlI.