Interactions with heparin-like molecules during erythrocyte invasion by Plasmodium falciparum merozoites

Michelle J. Boyle, Jack S. Richards, Paul R. Gilson, Wengang Chai, James G. Beeson

Research output: Contribution to journalArticleResearchpeer-review

108 Citations (Scopus)

Abstract

During erythrocyte invasion, Plasmodium falciparum merozoites use multiple receptor-ligand interactions in a series of coordinated events, but current knowledge of these interactions is limited. Using real-time imaging of invasion, we established that heparin-like molecules block early, and essential, events in erythrocyte invasion by merozoites. All P falciparum isolates tested, and parasites using different invasion pathways were inhibited to comparable levels. Furthermore, it was not possible to select for heparin-resistant parasites. Heparin-like molecules occur naturally on the surface of human erythrocytes, where they may act as receptors for binding of merozoite surface proteins. Consistent with this, we demonstrated that MSP1-42, a processed form of merozoite surface protein 1 (MSP1) involved in invasion, bound heparin in a specific manner; furthermore, binding was observed with the secondary processing fragment MSP1-33, but not MSP1-19. We defined key structural requirements of heparin-like molecules for invasion inhibition and interactions with MSP1-42. Optimal activity required a degree of sulfation more than or equal to 2, disulfation of the N-acetylglucosamine or hexuronic acid residue, and a minimum chain length of 6 monosaccharides. These findings have significant implications for understanding P falciparum invasion of erythrocytes and the development of novel therapeutics and vaccines.

Original languageEnglish
Pages (from-to)4559-4568
Number of pages10
JournalBlood
Volume115
Issue number22
DOIs
Publication statusPublished - 3 Jun 2010
Externally publishedYes

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