Plasmodium falciparum merozoite surface protein networks and host protein interactions

Malaria is caused by protozoan parasites of the genus Plasmodium and is responsible for significant morbidity and mortality in many tropical regions. Currently there is no vaccine available for malaria and resistance to anti-malarial agents is common.; Plasmodium parasites inhabit host erythrocytes. Several Plasmodium proteins that are believed to mediate the process of erythrocyte invasion have been identified, and are currently being evaluated as vaccine candidates in several laboratories; however, the exact role for most of these proteins in invasion is unclear. Additionally, once erythrocyte invasion has ensued several host-protein/parasite-protein interactions occur including several with host erythrocyte spectrin.; Here we have evaluated parasite-parasite-, and/or host-parasite-protein-protein interactions for several Plasmodium proteins including: merozoite surface protein-1 (MSP-1), MSP-3, MSP-6, MSP-7, apical membrane antigen-1 (AMA-1), acidic basic repeat antigen (ABRA), ring-infected erythrocyte antigen (RESA), and erythrocyte membrane protein-1 (EMP-1) in large- and small-scale yeast two-hybrid (Y2H) assays. Through our library-scale Y2H analysis we have identified a possible host-parasite protein-protein interaction for MSP-1 with human filamin (aka., actin-binding protein). Additionally, we have defined MSP-1/MSP-7- and MSP-1/MSP-6- interactions. We have also evaluated interactions between human erythroid spectrin domains/regions with MSP-1.83, EMP-1, and RESA, as well as possible MSP-3/ABRA interactions. The results of these studies may aid malaria vaccine design and drug development.