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. 2002 Nov 13;51(1):49–54. doi: 10.1016/0166-6851(92)90199-T

Binding of Plasmodium falciparum 175-kilodalton erythrocyte binding antigen and invasion of murine erythrocytes requires N-acetylneuraminic acid but not its O-acetylated form

Francis W Klotz 1, Palmer A Orlandi 1, Gerd Reuter 2, Stuart J Cohen 1, JDavid Haynes 1, Roland Schauer 2, Russell J Howard 3, Peter Palese 4, Louis H Miller 5,∗
PMCID: PMC7173321  PMID: 1565137

Abstract

Sialic acid on human erythrocytes is involved in invasion by the human malaria parasite, Plasmodium falciparum. Mouse erythrocytes were used as a reagent to explore the question of whether erythrocyte sialic acid functions as a nonspecific negative charge or whether the sialic acid is a necessary structural part of the receptor for merozoites. Human erythrocytes contain N-acetylneuraminic acid (Neu5Ac), whereas mouse erythrocytes, which are also invaded by P. falciparum merozoites, contain 9-O-acetyl-N-acetylneuraminic acid (Neu5,9Ac2) and N-glycoloylneuraminic acid (Neu5Gc), in addition to Neu5Ac. We compared the effects of sialidase and influenza C virus esterase treatments of mouse erythrocytes on invasion and the binding of a 175-kDa P. falciparum protein (EBA-175), a sialic acid-dependent malaria ligand implicated in the invasion process. Sialidase-treated mouse erythrocytes were refractory to invasion by P. falciparum merozoites and failed to bind EBA-175. Influenza C virus esterase, which converts Neu5,9Ac2 to Neu5Ac, increased both invasion efficiency and EBA-175 binding to mouse erythrocytes. Thus, the parasite and EBA-175 discriminate between Neu5Ac and Neu5,9Ac2, that is, the C-9 acetyl group interferes with EBA-175 binding and invasion by P.falciparum merozoites. This indicates that sialic acid is part of a receptor for invasion.

Keywords: Plasmodium falciparum, Red cell, Merozoite, Receptor, Sialic acid

Abbreviations: EBA-175, 175-kDa erythrocyte binding antigen; Neu5Ac, N-acetylneuraminic acid; Neu5Gc, N-glycoloylneuraminic acid; Neu5,9Ac2, 9-O-acetyl-N-acetylneuraminic acid

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