The global aquaculture industry faces multibillion USD losses each year due to diseases, particularly those caused by Vibrio spp., the major bacterial pathogens in aquatic animals. The use of antibiotics to control bacterial infections has led to the development and spread of resistance. Therefore, alternative methods are needed. As pathogens rely on virulence factors (i.e. compounds or cell structures that allow them to cause disease) to infect their host, preventing pathogens from producing them is an important alternative strategy, i.e. antivirulence therapy. In Vibrio cholerae, the ToxR regulon controls virulence gene expression in response to different signals. ToxR is present in Harveyi clade vibrios but little is known about its role in regulating the virulence of these pathogens. This project focusses on determining how the ToxR regulon influences the virulence of Harveyi clade vibrios by constructing a toxR deletion mutant. Furthermore, we will apply this knowledge in order to interfere with the ToxR regulon through small molecule inhibitors (virstatin analogues, unsaturated fatty acids and “second generation” indole analogues) to control disease caused by Harveyi clade vibrios. To assess the impact on the virulence of Harveyi clade vibrios, both in vitro and in vivo tests will be used. Finally, the commercial potential of the most promising inhibitors will be explored through lab-scale and commercial-scale trials with whiteleg shrimp.