Diseases caused by pathogenic vibrios cause major losses in aquaculture. The use of antibiotics in order to control these infections has led to the development and spread of antibiotic-resistant pathogens, rendering antibiotic treatments ineffective and causing problems for food safety. Therefore, novel methods to control vibriosis are needed. Recent research has shown that indole controls virulence-related phenotypes in pathogenic bacteria and indole is one of the cell-to-cell signaling molecules produced by vibrios. Consequently, we aimed at investigating the interference with indole signaling in order to control vibriosis in aquaculture.
We found that indole controls several virulence-related phenotypes in vibrios, most notably biofilm formation and motility. Further, we found that indole decreases the virulence to aquatic organisms in all marine vibrios studied thus far, including V. anguillarum (in sea bass), V. campbellii (in brine shrimp and giant river prawn), V. crassostreae (in blue mussel), acute hepatopancreatic necrosis disease (AHPND)-causing V. parahaemolyticus (in brine shrimp) and V. tasmaniensis (in blue mussel). At the tested concentrations, indole did not affect the growth of the vibrios. This is important because it indicates that there will be a lower risk for the spread of resistance against the virulence-decreasing effect of indole signaling when compared to antibiotics.
Given the fact that indole signaling controls the virulence of Vibrio species, we have been searching for more potent indole analogues to control vibriosis. Indole analogues are widely present in nature. Most notably is the auxin plant hormone indole-3-acetic acid. We found that indole-3-acetic acid decreases the biofilm formation and motility of V. campbellii, V. harveyi and V. parahaemolyticus strains and protects brine shrimp larvae from these pathogens. Moreover, addition of indole-3-acetic acid to the feed completely protected whiteleg shrimp from AHPND. Interestingly, auxins are not only produced by terrestrial plants, but also by algae and seaweeds. Hence, micro-algae and seaweeds could be interesting sources of auxins to control vibriosis in aquaculture.
In addition to natural indole analogues, we have also studied synthetic derivatives. A first group of derivatives are indene, 2,3-benzofuran and thianaphthene, in which the N atom of indole is replaced by C, O and S, respectively. All three of these compounds were found to increase the survival of brine shrimp larvae challenged with V. campbellii to around 80% or more. A second interesting group of synthetic indole analogues are halogenated indoles. We investigated the impact of 31 halogenated indoles on V. campbellii. Five of these compounds increased the survival of brine shrimp challenged with V. campbellii to over 80% when added at 10 µM.