Intracellular Survival of Protistan Parasites: Role(s) of the Host and Parasite Membrane Transporter Slc11a in the Competition for Iron

Perkinsus marinus是一种兼性的细胞内寄生虫，可引起东方牡蛎Crassostrea virgiica的“皮尔莫”病。在过去的几十年里，它对墨西哥湾和大西洋沿岸的牡蛎种群造成了广泛的破坏，对当地渔业和沿海水域的健康造成了灾难性的后果。Marinus在牡蛎血细胞内存活并增殖，这种血细胞通常会杀死潜在的病原体，最终压倒宿主。在调节寄生虫细胞内存活的因素中，可溶性铁是一个关键成分。寄生虫必须从宿主那里获得生长所必需的铁，而宿主必须保留铁，以防止病原体获得铁，并实现自身的基本细胞功能。这种对铁的“拉锯战”对寄生虫-宿主相互作用的结果至关重要。本研究的目的是研究近海对虾及其牡蛎宿主对铁的吸收途径。初步研究将集中在寄生虫(P.marinus Slc11a)和牡蛎(C.virginica Slc11a)中鉴定和克隆的膜铁转运蛋白，并将包括它们的详细分子和功能特征，试图将寄生虫和宿主铁转运蛋白的基因表达与内吞的Marinus命运联系起来。这些研究将大大增加对铁运输的基本了解，深入了解金属转运蛋白在宿主-寄生虫系统中的作用，并提供无脊椎动物防御机制和寄生虫逃避细胞内死亡的适应信息。拟议的研究包括重要的教育和培训活动。来自学校、学院和大学的两名兼职博士后实习生、一名研究生和学生实习生(特别是未被充分代表的少数民族)将参加。研究活动将适用于海洋生物科技中心的科学技术项目，该项目将把这种模式作为巴尔的摩地区K-12学生的科学教学工具。

Perkinsus marinus is a facultative intracellular parasite that causes "Dermo" disease in the eastern oyster Crassostrea virginica. In the past few decades it has produced extensive damage to oyster populations along the Gulf of Mexico and Atlantic coast, with catastrophic consequences for local fisheries and the health of coastal waters. P. marinus survives and proliferates inside the oyster hemocytes, blood cells that normally kill potential pathogens, eventually overwhelming the host. Among the factors that modulate the parasite's intracellular survival, soluble iron is a critical component. Parasites must acquire from their host the iron essential for growth, while the host must withhold iron to prevent pathogens from acquiring it, and for its own basic cellular functions. This "tug-of-war" for iron is fundamental to the outcome of parasite-host interactions. The goal of this research project is to characterize the iron uptake pathways in both P. marinus and its oyster host. Studies will be focused on membrane iron transporters identified and cloned in the parasite (P. marinus Slc11a) and the oyster (C. virginica Slc11a) during preliminary studies, and will consist of their detailed molecular and functional characterization, attempting to correlate gene expression of parasite and host iron transporters with the fate of endocytosed P. marinus. These studies will add significantly to the basic understanding of iron transport, provide insight into the role of metal transporters in host-parasites systems, and provide information on invertebrate defense mechanisms and parasites' adaptations to escape intracellular killing. The proposed studies encompass significant educational and training activities. Two part-time postdoctoral trainees, a graduate student, and student interns (particularly underrepresented minorities) from schools, colleges and universities will participate. Research activities will be adapted for conceptual and "hands-on" experiences for the SciTech program at the Center of Marine Biotechnology, which uses this model as a science-teaching tool for K-12 students from the Baltimore region.