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

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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.