Altered parasite life-cycle processes characterize Babesia divergens infection in human sickle cell anemia

Babesia divergens is an intra-erythrocytic parasite that causes malaria-like symptoms in infected people. As the erythrocyte provides the parasite with the infra-structure to grow and multiply, any perturbation to the cell should impact parasite viability. Support for this comes from the multitude of studies that have shown that the sickle trait has in fact been selected for because of the protection in provides against a related Apicomplexan parasite, Plasmodium that causes malaria. In this paper, we examine the impact of both sickle cell anemia and sickle trait RBC environment on different aspects of the B. divergens life-cycle and reveal that multiple aspects of parasite biological processes are altered in the mutant sickle cell anemia RBCs, including parasite population progression, the latter caused potentially by defective merozoite infectivity and/or defective egress from the sickle cell, resulting in severely lowered parasitemia in these cells with sickle cell anemia. In contrast, the sickle trait red cells provide a supportive environment permitting in vitro infection rates comparable to wild-type red cells. The elucidation of these naturally occurring red cell resistance mechanisms is needed to shed light on host-parasite interaction, lend evolutionary insights into these related blood-borne parasites and to provide new insights into the development of therapies against this disease.