title: An inhibitor of bacterial quorum sensing reduces mortalities caused by Vibriosis in rainbow trout (Oncorhynchus mykiss, Walbaum).
abstract: The fish pathogen Vibrio anguillarum produces quorum sensing signal molecules, N-acyl homoserine lactones (AHLs), which in several Gram-negative human and plant pathogenic bacteria regulate virulence factors. Expression of these factors can be blocked using specific quorum-sensing inhibitors (QSIs). The purpose of this study was to investigate the effect of a QSI, furanone C-30, on mortality of rainbow trout during challenge with V. anguillarum. Addition of 0.01 or 0.1 microM furanone C-30 to rainbow trout infected by cohabitation caused a significant reduction in accumulated mortality from 80-100% in challenge controls to 4-40% in treated groups. Furanone C-30 had no effect in an immersion challenge system, probably due to a very high water exchange and a rapid dilution of furanone C-30. Growth and survival of V. anguillarum were not affected by the concentrations of furanone C-30 used in the challenge experiments, thus avoiding selection for resistance. To elucidate the mechanism of disease control by furanone C-30, we determined its effect on the bacterial proteome, motility, and respiration. No effects were seen of furanone C-30 in any of these experiments. Although no cytotoxic effect on HeLa cells were observed, exposure to 1 microM (or higher) concentrations of furanone C-30 had detrimental effects on the rainbow trout. Our results indicate that QSIs can be used in non-antibiotic based control of fish diseases. However, they also underline the need for development of novel, less toxic QSI compounds and the need for understanding the exact mechanism(s) of action.
authors.affiliation: Danish Institute for Fisheries Research, Department of Seafood Research, Søltofts Plads, c/o Technical University of Denmark, Lyngby, Denmark.
authors.forename: Maria
authors.initials: M
authors.lastname: Rasch
authors.forename: Christiane
authors.initials: C
authors.lastname: Buch
authors.forename: Brian
authors.initials: B
authors.lastname: Austin
authors.forename: Wilhelmina J
authors.initials: WJ
authors.lastname: Slierendrecht
authors.forename: Kim S
authors.initials: KS
authors.lastname: Ekmann
authors.forename: Jens Laurits
authors.initials: JL
authors.lastname: Larsen
authors.forename: Charlotte
authors.initials: C
authors.lastname: Johansen
authors.forename: Kathrin
authors.initials: K
authors.lastname: Riedel
authors.forename: Leo
authors.initials: L
authors.lastname: Eberl
authors.forename: Michael
authors.initials: M
authors.lastname: Givskov
authors.forename: Lone
authors.initials: L
authors.lastname: Gram
mesh_terms: D015107:4-Butyrolactone / Q000031:analogs & derivatives* / Q000096:biosynthesis; D000818:Animals; D001426:Bacterial Proteins / Q000032:analysis; D004734:Energy Metabolism / Q000187:drug effects; D005393:Fish Diseases / Q000382:microbiology / Q000401:mortality*; D005663:Furans / Q000494:pharmacology / Q000627:therapeutic use* / Q000633:toxicity; D015964:Gene Expression Regulation, Bacterial; D006367:HeLa Cells; D006801:Humans; D009068:Movement / Q000187:drug effects; D017686:Oncorhynchus mykiss / Q000382:microbiology*; D020543:Proteome; D014733:Vibrio / Q000187:drug effects* / Q000472:pathogenicity* / Q000502:physiology; D014735:Vibrio Infections / Q000382:microbiology / Q000401:mortality / Q000662:veterinary*; D037521:Virulence Factors / Q000096:biosynthesis / Q000235:genetics
chemical_list: D001426:Bacterial Proteins; D005663:Furans; D020543:Proteome; D037521:Virulence Factors; C494198:furanone C-30; C088386:homoserine lactone; D015107:4-Butyrolactone