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Evolutionary Biology of Parasitism
Published in Eric S. Loker, Bruce V. Hofkin, Parasitology, 2023
Eric S. Loker, Bruce V. Hofkin
Perhaps, though, it might be advantageous to select a mate with a particular MHC allele effective against a very common local parasite? Some studies with three-spined stickleback fish (Gasterosteus aculeatus) suggest females prefer to mate with males that carry a particular MHC variant useful in countering infection with a common parasite, the monogenean Gyrodactylus salaris.
Interactive associations between fish hosts and monogeneans
Published in G. F. Wiegertjes, G. Flik, Host-Parasite Interactions, 2004
Kurt Buchmann, Thomas Lindenstrøm, Jose Bresciani
Evidence has been presented which suggests involvement of immunological elements in determination of host specificity. Corticosteroids are generally assumed to inhibit a range of immunological elements in mammals. That a similar situation exists for salmonids has indeed been indicated by the experimental inhibition of multiplication and metabolism of rainbow trout macrophages (Pagniello et al., 2002). These authors found that cortisol and dexamethasone are compounds with a marked influence on these macrophage functions in rainbow trout and Zou et al. (2000) detected impairment of IL-1 production in cortisol-treated rainbow trout macrophages. These observations do indeed suggest a connection between host specificity and immunity. Studies using treatment of salmonid hosts with immuno-suppressants, such as hydrocortisone and dexamethasone, showed that unsuitable parasites could colonize the treated host with greater success compared to untreated controls. Thus, two races of Atlantic salmon, Salmo salar, which are unsuitable hosts for Gyrodactylus derjavini, allowed increased population growth following dexamethasone administration (Olafsdottir et al., 2003). Further, these parasites often aggregate on the cornea of unsuitable hosts. The cornea is regarded as an immuno-privileged site due to lack of mucous cells and mast cells in this cell layer (Buchmann and Bresciani, 1998; Sigh and Buchmann, 2000). Interestingly, in immuno-suppressed hosts the unsuitable parasites did not aggregate on the corneal surface to the same extent as seen in responding hosts (Olafsdottir et al., 2003). Other studies have shown that brown trout Salmo trutta, which is an unsuitable host for Gyrodactylus salaris (Bakke et al., 1999) become significantly more susceptible to this species following hydrocortisone acetate administration (Harris et al., 2000). The finding that trout complement exists in various forms with different binding abilities (Sunyer et al., 1997, 1998; Zarkadis et al., 2001) suggests that these molecules may be part of the immunologically relevant recognition molecules. Although these matters are relatively well described it should be noted that genes for a range of additional acute-phase molecules are expressed upon infection of a fish (Bayne et al., 2001). It cannot be excluded that such substances will play a role in the interactions between monogeneans and fishes.
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
The Monogenean platyhelminth Gyrodactylus salaris, a fish parasite of salmon and other economically relevant aquaculture fish species, encodes for a β-class CA, GsaCAβ, which has been investigated here for its inhibition profile with sulphonamides/sulfamates, as a possible antiparasitic drug target. We identified several effective GsaCAβ inhibitors, belonging to simple heterocyclic sulphonamide derivatives, the deacetylated precursors of acetazolamide and methazolamide, which showed KI values of 81.9 − 139.7 nM. Many other simple benezenesulfonamides and clinically used agents, such as acetazolamide, methazolamide, ethoxzolamide, dorzolamide, benzolamide, sulthiame and hydrochlorothiazide showed inhibition constants <1 µM. The least effective GsaCAβ inhibitors were 4,6-disubstituted-1,3-benzene disulfonamides, with KIs in the range of 16.9 − 24.8 µM. Although no GsaCAβ-selective inhibitors were detected so far, this preliminary investigation may be helpful for better understanding the SAR for inhibition of this parasite enzyme and for the potential development of more effective and eventually parasite-selective inhibitors.
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.