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Avian coccidiosis: a disturbed host-parasite relationship to be restored
Published in G. F. Wiegertjes, G. Flik, Host-Parasite Interactions, 2004
The stages that are responsible for the induction of the immunity can be different from the targets of the effector branch of the immune system. From studies with irradiated oocysts or sporozoites, that could invade host cells but not proliferate, it was shown that early development is determining the induction of the appropriate immune response possibly due to the correct presentation of antigens in the context of class I MHC (Jenkins, 1991a, b). These results were corroborated by investigations using precocious strains, that have a shortened life cycle due to absence of one or more mitotic stages, that showed that first-generation schizonts were more immunogenic when compared on biomass than later developmental stages (McDonald et al., 1988). From our own work using Toltrazuril (Baycox) as a drug to kill intracellular stages (Greif, 2000) it was shown that when giving the drug already 24 h prior to infection a protective immunity could be induced at rather low dosages of inoculation of E. tenella or E. acervulina oocysts (see Table 2). At a low dose of 100 oocysts E. acervulina a reduction of protection (only 50%) seems to have been induced when the first generation was allowed to complete its proliferation. This suggests that these first stages are immunosuppressive to some extent. In all, these data show that indeed the sporozoite and/or the first intracellular stage is decisive for good induction of immunity.
Sulphonamide inhibition studies of the β-carbonic anhydrase GsaCAβ present in the salmon platyhelminth parasite Gyrodactylus salaris
Published in Journal of Enzyme Inhibition and Medicinal Chemistry, 2023
Ashok Aspatwar, Alessandro Bonardi, Heidi Aisala, Ksenia Zueva, Craig R Primmer, Jaakko Lumme, Seppo Parkkila, Claudiu T. Supuran
We have recently reported the cloning and characterisation of a β-class carbonic anhydrase (CA, EC 4.2.1.1) encoded in the genome of Gyrodactylus salaris, GsaCAβ1, a platyhelminth (flatworm) parasite attacking various fish species2,3. The Atlantic salmon (Salmo salar) is particularly sensitive to this parasite, which produced catastrophic losses in fish farms in Scandinavian countries and elsewhere, starting with the 1970s3–5. By releasing proteolytic enzymes, the parasite attaches on the fish gills, fins or skin inducing the formation of wounds, which favour the emergence of infections, with debilitation and eventual death of the infected animals5,6. There are no effective drugs for the treatment of this parasitic disease, although a variety of inorganic salts, synthetic compounds/drugs (e.g., praziquantel, levamisole, mebendazole and toltrazuril) and other approaches (manual removal of the worms) have been investigated, with rather unsuccessful results7. Furthermore, many of these compounds/drugs induce serious host toxicity, raising thus significant human health concerns if such fish is to be consumed7. Thus, as for other platyhelminth parasites producing infection in vertebrates including humans, such as Schistosoma haematobium8 or Schistosoma mansoni9–11 there is a stringent need of alternative drug targets and efficient compounds to treat these infections.
Cloning, purification, kinetic and anion inhibition studies of a recombinant β-carbonic anhydrase from the Atlantic salmon parasite platyhelminth Gyrodactylus salaris
Published in Journal of Enzyme Inhibition and Medicinal Chemistry, 2022
Ashok Aspatwar, Harlan Barker, Heidi Aisala, Ksenia Zueva, Marianne Kuuslahti, Martti Tolvanen, Craig R. Primmer, Jaakko Lumme, Alessandro Bonardi, Amit Tripathi, Seppo Parkkila, Claudiu T. Supuran
Gyrodactylus salaris is a flatworm (platyhelminth) parasite belonging to the Monogeneans group, which are hermaphrodite ectoparasites found on the gills, fins, or skin of fish1,2. They do not need an intermediate host for infecting a range of fish species, some of which possess significant commercial status, such as the Atlantic salmon (Salmo salar) and related species3,4. The presence of this parasitic pathogen has been reported in 19 countries across Europe and has already produced catastrophic losses of Atlantic salmon mainly in Norway starting in the 1970s and in Russian Karelia since 19921–4. This small (0.5 mm) parasite attacks the host by attaching its anterior end to the fish through secretions from the cephalic glands, and then releasing a digestive solution rich in proteolytic enzymes which dissolves the fish skin, inducing the formation of large wounds which favour secondary infections5. A variety of inorganic and organic compounds, among which are salt (NaCl), hypochlorite, permanganate, aluminium salts, praziquantel, levamisole, mebendazole, toltrazuril, etc., have been tested for efficacy against a broad spectrum of monogenean species, including G. salaris, but only trichlorfon and dichlorvos (Figure 1) showed some efficacy6,7. However, both compounds act as irreversible organophosphoric acetylcholinesterase inhibitors, showing thus a rather high toxicity for all vertebrates, not only for fish8.