Bacterial diseases cause major losses in food production in general, and in aquaculture in specific. At
this moment, antibiotics are often the only therapeutics farmers have to protect their animals.
However, the frequent use of antibiotics in aquaculture has resulted in the development and spread
of antibiotic resistance, and aquaculture is a major source of antibiotic resistance genes in human
pathogens. Antibiotic resistant infections are currently the second leading cause of death worldwide
and the WHO predicts that the situation will become even worse in the near future if no adequate
measures are undertaken, with 10 million deaths per year by 2050, and a cumulative loss to the
world’s GDP of $100 trillion. Hence, novel therapeutics are needed in order to assure food security
in the future, and at the same time improve food safety. In this project, we will perform pioneering
research on the development of antivirulence therapy (the “disarming” of pathogens rather than
killing them), based on the interference with indole signaling (a mechanism that is required for full
virulence of bacterial aquaculture pathogens). Specifically, we will screen a library of commercially
available indole analogues for increased antivirulence activity when compared to indole. We will
thus establish structure-activity relations with respect to the antivirulence activity of indoles, in this
way opening the road to the development of novel, highly active virulence inhibitors.