Ancient human sialic acid variant restricts an emerging zoonotic malaria parasite

作者：Dankwa Selasi; Lim Caeul; Bei Amy K; Jiang Rays H Y; Abshire James R; Patel Saurabh D; Goldberg Jonathan M; Moreno Yovany; Kono Maya; Niles Jacquin C; Duraisingh Manoj T^*

来源：Nature Communications, 2016, 7(1): 11187.

DOI：10.1038/ncomms11187

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, PkDBPb and PkDBPg, 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, PkDBPa and loss of PkDBPg. 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.

• 出版日期2016-4