Sialic acid specificity of erythrocyte binding Antigen-140 orthologues in human- and ape-infective Laverania species.

Plasmodium falciparum is the only human-infective species within the Laverania subgenus. In order for Plasmodium falciparum merozoites to invade erythrocytes, parasite ligands interact with a number of erythrocyte surface proteins, several of which are modified with sialic acids. These sialic acids differ between humans, which can synthesise only Neu5Ac sialic acids, and apes which express an enzyme absent in humans that converts Neu5Ac to Neu5Gc, resulting in their surface sialoglycoproteins predominantly being modified with Neu5Gc. This difference between apes and humans has been previously proposed to play a role in the specificity of ligand-receptor interactions between Laverania species. In this study we used biochemical and experimental genetic approaches to explore the molecular preferences of one specific invasion ligand, EBA-140. Recombinant EBA-140 ligands from P. falciparum (human-infective), P. praefalciparum (gorilla-infective) and P. reichenowi (chimpanzee-infective), were all able to bind both sialic acids, but all showed a clear preference for Neu5Gc. Using CRISPR/Cas9 to swap the receptor-binding region of P. falciparum EBA-140 with the same region from Laverania orthologues had no effect on parasite growth or invasion in chimeric transgenic lines. There is therefore no evidence that Neu5Ac/Neu5Gc specificity plays a role in host preference for EBA-140 orthologues.