A C2 domain containing plasma membrane protein of Plasmodium falciparum merozoites mediates calcium-dependent binding and invasion to host erythrocytes.

BACKGROUND

Invasion of red blood cells by Plasmodium falciparum merozoites is governed by multiple receptor-ligand interactions which are critical for bridging the two cells together. The critical function of these ligands for invasion and their direct exposure to the host immune system makes them lucrative vaccine candidates. This necessitates the discovery of new adhesins with less redundancy that mediates the binding of merozoite to the red cell, and furthermore invasion into it. Here we have identified a novel membrane associated antigen (PfC2DMA) that is conserved throughout the Plasmodium species and has a membrane targeting C2 domain at its extreme N-terminal region.

METHODS

Recombinant C2 was expressed heterologously in bacteria and purified to homogeneity. Mice antisera against C2 was raised and used to check the expression and intraparasitic localization of the protein. RBC and Ca ion binding activity of C2 was also checked.

RESULTS

C2 exhibited specific binding to Ca ions and not to Mg ions. PfC2DMA localized to the surface of merozoite and recombinant C2 bound to the surface of human RBCs. RBC receptor modification by treatment with different enzymes showed that binding of C2 to RBC surface is neuraminidase sensitive. Mice antisera raised against C2 of Pf C2DMA showed invasion inhibitory effects.

CONCLUSION

Our findings suggest that C2 of PfC2DMA binds to surface of red cell in a Ca-dependent manner, advocating a plausible role in invasion and can serve as a potential novel blood stage vaccine candidate.