Repurposing trypanocidal drugs to tackle amoebic gill disease in Atlantic Salmon
An outbreak of amoebic gill disease in Ireland
Farmed Atlantic salmon affected by AGD exhibiting multifocal patches of swollen gill tissue
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Source: The veterinary record :139(14):348-9
Neoparamoeba perurans in the culture media
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Source: Dr. Ronnie Mooney, University of west Scotland
Paramoeba and its kinetoplastid endosymbiont Perkinsela. a) Paramoeba sp. cells stained with haematoxylin and eosin in histological sections of gill tissue of Salmo salar
(NP = nucleus of the host amoeba; En = Perkinsela sp. endosymbiont). b) Trophozoites of P. pemaquidensis in hanging drop preparations under Nomarski differential interference contrast microscopy.
Amoebic gill disease (AGD), caused by Neoparamoeba perurans, is as a major disease in salmonid aquaculture, with annual associated losses (20%) rapidly approaching those caused by caligid sea lice. N. perurans has a unique cellular biology that can readily exploited given the right tools.
Enclosed with in the cytoplasm is an endosymbiotic kinetoplastid called Perkinsela. Genome sequence 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 interdependence between host and symbiont.
Using our existing state-of the-art drug discovery pipeline for kinetoplastids, we propose 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 killing the endosymbiont will lead to death of its host. A candidate drug will then be tested for activity against amoebic gill disease in vivo at a marine trial site operated by the Marine Institute (MI), Ireland.
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 by opening new markets for their use.
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Partners
UKRI and Wellcome funded drug discovery pipeline at the University of
Glasgow (metabolomics, pharmacology and drug toxicity)
Marine Institute (MI), Ireland (In vivo trials)
University of Glasgow
MSD Animal Health
Scottish Sea Farms
PI, Prof. Mike Barrett, University of Glasgow, UK
Prof. Phil McGinnity, Marine Institute, Ireland
Dr. Neil Ruane, Marine Institute, Ireland
Collaborators
Prof. John Archibald, Dalhousie University, Canada
Prof. Mathew Cook, CSIRO Agriculture and Food, Australia
Prof. Samuel Martin, University of Aberdeen, UK
Prof. Fiona Hernandez, University of West Scotland, UK
Dr. Roderick Williams, University of West Scotland, UK