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

牡蛎和蛤蜊不仅是具有很高商业价值的贝类资源，也是美国河口和海岸环境的重要组成部分。因此，这些双壳类动物的传染病对贝类产业和环境健康都有严重的影响。在影响美国贝类的几种疾病中，Perkinsus （Dermo）寄生虫已在天然和养殖牡蛎种群中造成严重死亡，迄今为止尚未开发出有效的预防或治疗方案。对于大多数贝类疾病，人们对寄生虫对宿主、感染和传播的特异性机制知之甚少。在之前的研究中，研究人员发现，Perkinsus寄生虫破坏宿主防御蛋白（凝集素），进入牡蛎细胞并引起疾病。现在，他们将阐明东部牡蛎和软壳蛤的凝集素如何决定不同波金索斯物种的宿主特异性，它们如何调节牡蛎和蛤体内寄生虫的生存，以及它们如何对免疫细胞的功能产生负面影响。这一信息对于理解不同的珀金苏氏菌是如何以及为什么对某些贝类或多或少具有致病性至关重要。这一基本知识将使创新方法的发展，以防止感染，寄生虫的致病作用，并将其传播给健康的贝类种群。将积极开展教育和培训方面的工作，特别是纳入人数不足的少数民族和妇女。所获得的基本知识将有助于对农业感兴趣的动物和人类的寄生虫病有新的认识。与对东部牡蛎具有高致病性的marinus相反，最初从软壳蛤Mya arenaria中分离出来的同源P. chesapeaki也可以存在于牡蛎中，但几乎没有证据表明其致病性。先前的研究发现，在东牡蛎中有两种对P. marinus有较强识别能力，但对P. chesapeaki有较弱识别能力；蛤蜊表达一种具有明显特异性的凝集素。这导致了一种假设，即珀金索属物种的宿主偏好和致病性与半凝集素介导的宿主进入，以及感染后调节血细胞功能和半凝集素表达的能力直接相关。这一假设将通过分子、遗传、生化、结构和细胞生物学的方法进行验证，以阐明：(a)牡蛎和蛤蜊凝集素对Perkinsus spp的鉴别识别的结构基础；(b)半乳糖凝集素介导的Perkinsus spp差异识别对调理、吞噬和血细胞内寄生虫存活的影响；(c)凝集素结合寄生虫和血细胞表面受体和共受体介导的机制，以及调节血细胞功能的信号通路的调节。因此，所提出的活性将高度改变长期以来的观念，即寄生虫模仿是一种避免被宿主识别的策略，而所提出的模型将揭示寄生虫获得糖相似不仅旨在促进宿主对进入和致病性的识别，而且具有必要的特异性来确定宿主的偏好。

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.