Galectins of the eastern oyster (C. virginica) and softshell clam (M. arenaria) as determinants for host preference and pathogenicity of sympatric Perkinsus parasite species

University Of Maryland At Baltimore, Baltimore

Investigators

Abstract

Oysters and clams constitute not only shellfishery resources of high commercial value, but also very important components of the estuarine and coastal environment in the USA Therefore, infectious diseases in these bivalve species have serious impacts in both the shellfisheries industry and health of the environment. Among the several diseases that affect shellfish in the USA, Perkinsus (Dermo) parasites have caused severe mortalities in natural and farmed oyster populations and no effective preventive or therapeutic solutions have been developed so far. For most shellfish diseases, little is known about the mechanisms of parasite specificity for the host, infection, and transmission. During prior studies the investigators discovered that Perkinsus parasites subvert a host defense protein (galectin) to gain entry in the oyster cells and cause disease. Now they will elucidate how the eastern oyster and softshell clam galectins determine the host specificity of the different Perkinsus species, how they modulate the survival of the parasite in oyster and clams, and how they negatively affect the functions of the immune cells. This information will be critical to understand how and why the different Perkinsus species are more or less pathogenic for certain shellfish species. This fundamental knowledge will enable the development of innovative methods to prevent infections, pathogenic effects of the parasites, and their transmission to healthy shellfish populations. Educational and training aspects will be actively pursued specifically incorporating underrepresented minorities and women. The fundamental knowledge obtained will contribute new insight into parasitic disease in animals of agricultural interest and man. In contrast with Perkinsus marinus that is highly pathogenic for eastern oysters, the sympatric P. chesapeaki, initially isolated from the softshell clam Mya arenaria, can also be present in oysters but there is little evidence of pathogenicity. Prior studies revealed in the eastern oyster two opsonic galectins that strongly recognize P. marinus, but weakly recognize P. chesapeaki; the clam expresses a galectin of distinct specificity. This led to the hypothesis that host preference and pathogenicity of Perkinsus species is directly related to galectin-mediated host entry, and ability to modulate hemocyte function and expression of galectins upon infection. This hypothesis will be tested by using molecular, genetic, biochemical, structural and cell biology approaches to elucidate: (a) the structural basis for differential recognition of Perkinsus spp by the oyster and clam galectins; (b) the effects of galectin-mediated differential recognition of Perkinsus spp on opsonization, phagocytosis, and intrahemocytic parasite survival; and (c) the mechanisms mediated by galectin binding to parasite and hemocyte surface receptors and co-receptors and the modulation of signaling pathways that regulate hemocyte function(s). Thus, the proposed activity will be highly transformative of the long-held concept that parasite mimicry is a strategy to avoid recognition by the host, while the proposed model would reveal acquisition of glycomimicry by the parasite aimed not only at promoting host recognition for entry and pathogenicity, but with necessary specificity to determine host preference.