a quorum sensing-disrupting brominated thiophenone with a promising therapeutic potential to treat luminescent vibriosis法定人数sensing-disrupting溴化thiophenone发光弧菌病治疗与一个有前途的治疗潜力.pdfVIP

A Quorum Sensing-Disrupting Brominated Thiophenone with a Promising Therapeutic Potential to Treat Luminescent Vibriosis 1 2 3 3 1 Tom Defoirdt *, Tore Benneche , Gilles Brackman , Tom Coenye , Patrick Sorgeloos , Anne Aamdal Scheie4 1 Laboratory of Aquaculture Artemia Reference Center, Ghent University, Ghent, Belgium, 2 Department of Chemistry, Faculty of Chemistry, University of Oslo, Oslo, Norway, 3 Laboratory of Pharmaceutical Microbiology, Ghent University, Ghent, Belgium, 4 Department of Oral Biology, Faculty of Dentistry, University of Oslo, Oslo, Norway Abstract Vibrio harveyi is amongst the most important bacterial pathogens in aquaculture. Novel methods to control this pathogen are needed since many strains have acquired resistance to antibiotics. We previously showed that quorum sensing- disrupting furanones are able to protect brine shrimp larvae against vibriosis. However, a major problem of these compounds is that they are toxic toward higher organisms and therefore, they are not safe to be used in aquaculture. The synthesis of brominated thiophenones, sulphur analogues of the quorum sensing-disrupting furanones, has recently been reported. In the present study, we report that these compounds block quorum sensing in V. harveyi at concentrations in the low micromolar range. Bioluminescence experiments with V. harveyi quorum sensing mutants and a fluorescence anisotropy assay indicated that the compounds disrupt quorum sensing in this bacterium by decreasing the ability of the quorum sensing master regulator LuxR to bind to its target promoter DNA. In vivo challenge tests with gnotobiotic brine shrimp larvae showed