Antibiotic resistant infections are currently the second cause of death worldwide, and aquaculture is a major source of antibiotic resistance genes in human pathogens. The aquaculture industry plays an important role in the world’s food supply. However, bacterial diseases cause major problems in aquaculture, with annual losses in the range of several billion US$. Controlling bacterial diseases in aquaculture is therefore essential for food security. However, the current practice of using antibiotics for this purpose is causing major problems with respect to food safety. Hence, the development of novel therapeutics to control bacterial diseases is an urgent societal challenge. Antisense technology, blocking gene expression in a sequence-specific manner, is well established in eukaryotes. In this project, we will develop a peptide nucleic acids (PNAs)-based antisense technology for sequence-specific inactivation of virulence (regulatory) genes in bacteria, thus opening up a completely novel arsenal of disease control agents. We will use Vibrio campbellii, one of the major aquaculture pathogens and a model species with respect to virulence regulation in bacteria, as model organism. We will validate the use of antisense PNAs to control disease in a highly controlled host model with gnotobiotic brine shrimp larvae. The findings obtained in this project will be directly relevant to aquaculture, but will also have implications reaching beyond aquaculture.