27041489

PMC4822025

Plasmodium knowlesi is a zoonotic parasite transmitted from macaques causing malaria in humans in Southeast Asia. Plasmodium parasites bind to red blood cell (RBC) surface receptors, many of which are sialylated. While macaques synthesize the sialic acid variant N-glycolylneuraminic acid (Neu5Gc), humans cannot because of a mutation in the enzyme CMAH that converts N-acetylneuraminic acid (Neu5Ac) to Neu5Gc. Here we reconstitute CMAH in human RBCs for the reintroduction of Neu5Gc, which results in enhancement of P. knowlesi invasion. We show that two P. knowlesi invasion ligands, PkDBPβ and PkDBPγ, bind specifically to Neu5Gc-containing receptors. A human-adapted P. knowlesi line invades human RBCs independently of Neu5Gc, with duplication of the sialic acid-independent invasion ligand, PkDBPα and loss of PkDBPγ. Our results suggest that absence of Neu5Gc on human RBCs limits P. knowlesi invasion, but that parasites may evolve to invade human RBCs through the use of sialic acid-independent pathways.

CDC Public Access

1DP2OD007124/OD/NIH HHS/United States
2-T32-AI007535-12/AI/NIAID NIH HHS/United States
5-K12-HD000850/HD/NICHD NIH HHS/United States
5-T32-GM08334/GM/NIGMS NIH HHS/United States
AI091787/AI/NIAID NIH HHS/United States
P50-GM098792/GM/NIGMS NIH HHS/United States
R36-CK000119-01/CK/NCEZID CDC HHS/United States
T32 GM008334/GM/NIGMS NIH HHS/United States