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 that thiophenone compound TF310, (Z)-4-((5-(bromomethylene)-2-oxo-2,5-dihydrothiophen-3-yl)methoxy)-4-oxobutanoic acid, completely protected the larvae from V. harveyi BB120 when dosed to the culture water at 2.5 µM or more, whereas severe toxicity was only observed at 250 µM. This makes TF310 showing the highest therapeutic index of all quorum sensing-disrupting compounds tested thus far in our brine shrimp model system.
Highlights
Vibrio harveyi, the causative agent of luminescent vibriosis, is one of the most important pathogens of aquatic animals, causing significant losses in the aquaculture industry worldwide [1]
Bioluminescence is one of the phenotypes that is regulated by the V. harveyi quorum sensing system and in a first experiment, the impact of the thiophenones on the bioluminescence of V. harveyi was determined
Wild type strain BB120 was grown to high cell density in order to activate quorum sensingregulated bioluminescence, after which the thiophenones were added to the medium at 2.5 mM
Summary
The causative agent of luminescent vibriosis, is one of the most important pathogens of aquatic animals, causing significant losses in the aquaculture industry worldwide [1]. Because of the development and spread of antibiotic resistance in these bacteria, antibiotic treatments are becoming inefficient and alternative control strategies are being developed [2]. One of these strategies is the disruption of quorum sensing, bacterial cell-to-cell communication. V. harveyi quorum sensing has been found to control biofilm formation [3] and the expression of different virulence factors, including a type III secretion system [4], extracellular toxin [5], metalloprotease [6], siderophore [7], chitinase [8] and phospholipase [9]. We found that virulence of the bacterium towards different aquatic organisms, including brine shrimp, is regulated by its quorum sensing system [10]
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