Parasites that live in red cells have rather ingenious ways of gaining entry into these cells, thus escaping the dangers of the host immune system. Research in the Laboratory of Blood-Borne Parasites focuses on the molecular mechanisms of red cell invasion of two Apicomplexan pathogens that invade the same human host cell, the red blood cell: Plasmodium falciparum, that causes malaria and Babesia divergens, that is the cause of babesiosis. Babesiosis is one of the most common infections of free living animals worldwide and is gaining increasing interest as an emerging zoonosis, which is a disease communicable from animals to humans. Our laboratory exploits the enormous explosion of knowledge seen recently in malaria, to extract analogous information on the invasion process of B. divergens, to facilitate a molecular comparison of the process between these two parasites, one that is specific to humans and the other that is zoonotic. Thus, it also represents a starting point to understand pathways of RBC invasion that support this zoonosis and may shed light on how zoonotic pathogens have evolved to transcend the species barrier to infect man. Additionally, because of the parallels in the invasion patterns of Plasmodium and Babesia into RBC's, we have a keen interest in developing B.divergens as a model to study RBC invasion in malaria. Two of the major difficulties of studying P.falciparum invasion can be overcome in the B.divergens invasion assay system, namely, the ease of obtaining high parasitemia (>90%) and the fact that infectious free merozoites are obtained in B. divergens cultures. Thus, our research could impact malaria studies as well.
Our immediate research focuses on the study of parasite ligand-RBC receptor interactions and how these facilitate the entry of both the P. falciparum and the B. divergens merozoite into the human erythrocyte. Babesiosis is fast becoming an important parasitosis because of two factors: (1) that Babesia is now recognized as a zoonotic parasite , with humans acquiring infections from mammalian animal reservoirs; and (2) that Babesia represents a potential threat to the blood supply for transfusions since asymptomatic infections in humans are common and the spread of parasite via blood transfusions has been frequently reported. We have already begun to exploit the wealth of information available for the Plasmodium system to extract data from B. divergens using a combination of comparative functional genomics. Preliminary data obtained by us so far shows a significant overlap in structural and functional aspects of the invasion machinery between these two hemoparasites, including the use of glycophorins as host receptors, the presence of invasion ligand homologs like AMA-1 and the use of subtilisin like proteases for successful invasion. Our research will contribute to a fundamental understanding of the biology of invasion which is the critical step in the life cycle of both Plasmodium and Babesia. The inhibition of RBC invasion by these parasites would prevent infection and consequently disease. Therefore, identification and characterization of the molecules, including ligand-receptor interactions and the proteases that participate in this step, is critical for the development of diagnostic tools, new drugs or vaccines against malaria and babesiosis.