Discussion

Amoebic gill disease (AGD), caused by Neoparamoeba perurans, is as a threatening disease in salmonid aquaculture associated with substantial annual losses (20%). The amoeba N. perurans has a unique cellular and evolutionary biology that can readily exploited given the right molecular tools. Enclosed in the cytoplasm N. perurans hosts an endosymbiotic aflagelate kinetoplastid called Perkinsela or Perkinsela-Like Organism (PLO). Genome sequence of this indicates that the basic physiology of the kinetoplastid endosymbiont contains many of the same biochemical features as those found in other kinetoplastid pathogens of man and domestic livestock (Trypanosoma brucei sp., T. cruzi, Leishmania sp.), as well as a high level of metabolic interdependence between host and symbiont. After Omics characterization of the functional associations between host and its endosymbiont, our existing state-of the-art drug discovery pipeline for kinetoplastids, the aim of this project is to test the potency of existing licensed and experimental drugs used against the kinetoplastid diseases for activity against N. perurans in culture, working on the hypothesis that inhibiting or killing the endosymbiont will lead to the death of its host. A candidate drug will then be tested for activity against amoebic gill disease in vivo. Drug residue accumulation in sediment samples at the trial site will be established to assay the potential environmental impact of therapeutant use. In addition to providing a much-needed new tool for aquaculture, our approach, which aims to repurpose drugs effective against neglected tropical disease but often too expensive to deploy, has the potential drive down their cost. Keywords: endosymbiosis, kinetoplastid, amoeba, amoebic gill disease, Omics