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较高商业价值的贝类渔业资源，也是美国河口和沿海环境的重要组成部分，因此这些双壳贝类的传染病对贝类渔业和环境健康产生严重影响。在影响美国贝类的几种疾病中，Perkinsus（Dermo）寄生虫已导致天然和养殖牡蛎种群的严重死亡，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，很少有人知道寄生虫对宿主的特异性，感染和传播的机制。在之前的研究中，研究人员发现帕金虫寄生虫破坏宿主防御蛋白（半乳糖凝集素）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半乳糖凝集素如何决定不同帕金虫物种的宿主特异性，它们如何调节牡蛎和蛤中寄生虫的生存，以及它们如何对免疫细胞的功能产生负面影响。这些信息对于理解不同的帕金苏斯物种如何以及为什么对某些贝类物种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，及其传播到健康的贝类种群。将积极开展教育和培训方面的工作，特别是吸收代表性不足的少数民族和妇女参加。所获得的基本知识将有助于新的见解寄生虫病的动物的农业利益和人。与帕金斯marinus是高致病性的东方牡蛎，同域P. chesapeaki，最初从软壳蛤Mya arenaria分离，也可以存在于牡蛎，但几乎没有证据表明致病性。先前的研究显示，在东部牡蛎两个调理半乳糖凝集素，强烈识别P. marinus，但弱识别P. chesapeaki;蛤表达的半乳糖凝集素的独特的特异性。这导致了这样的假设，即帕金虫属物种的宿主偏好和致病性与半乳糖凝集素介导的宿主进入以及在感染后调节血细胞功能和半乳糖凝集素表达的能力直接相关。这一假设将通过使用分子、遗传、生物化学、结构和细胞生物学方法来验证，以阐明：（a）牡蛎和蛤半乳糖凝集素对帕金虫属的差异识别的结构基础;（B）半乳糖凝集素介导的帕金虫属的差异识别对调理作用、吞噬作用和血细胞内寄生虫存活的影响;和（c）半乳糖凝集素与寄生虫和血细胞表面受体和辅助受体结合所介导的机制，以及调节血细胞功能的信号传导途径的调节。因此，拟议的活动将是高度变革的长期持有的概念，寄生虫模仿是一种策略，以避免识别的主机，而拟议的模型将揭示收购glycomimicry的寄生虫，目的不仅是促进主机识别进入和致病性，但必要的特异性，以确定主机的偏好。

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.