Interactions with heparin-like molecules during erythrocyte invasion by Plasmodium falciparum merozoites
- Author(s)
- Boyle, MJ; Richards, JS; Gilson, PR; Chai, WG; Beeson, JG;
- Details
- Publication Year 2010-06-03,Volume 115,Issue #22,Page 4559-4568
- Journal Title
- BLOOD
- Publication Type
- Journal Article
- 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. (Blood. 2010; 115(22): 4559-4568)
- Publisher
- AMER SOC HEMATOLOGY
- Keywords
- RED-BLOOD-CELLS; K5 POLYSACCHARIDE DERIVATIVES; APICAL MEMBRANE ANTIGEN-1; SURFACE PROTEIN-1 MSP1; MALARIA PARASITE; INHIBITORY ANTIBODIES; IN-VITRO; SERINE-PROTEASE; CURDLAN SULFATE; COMPLEX
- Publisher's Version
- https://doi.org/10.1182/blood-2009-09-24372
- Terms of Use/Rights Notice
- Refer to copyright notice on published article.
Creation Date: 2010-06-03 12:00:00