Skidmore, MA and Mustaffa, KMF and Cooper, LC and Guimond, SE and Yates, EA and Craig, AG (2017) A semi-synthetic glycosaminoglycan analogue inhibits and reverses Plasmodium falciparum cytoadherence. PLoS One, 12 (10). e0186276 - ?. ISSN 1932-6203

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Abstract

A feature of mature Plasmodium falciparum parasitized red blood cells is their ability to bind surface molecules of the microvascular endothelium via the parasite-derived surface protein Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1). This ligand is associated with the cytoadherence pathology observed in severe malaria. As pRBC treated with effective anti-malarial drugs are still able to cytoadhere, there is therefore a need to find an adjunct treatment that can inhibit and reverse the adhesion process. One semi-synthetic, sulfated polysaccharide has been identified that is capable of inhibiting and reversing sequestration of pRBC on endothelial cells in vitro under physiological flow conditions. Furthermore, it exhibits low toxicity in the intrinsic (APTT assay) and extrinsic (PT assay) clotting pathways, as well as exhibiting minimal effects on cell (HUVEC) viability (MTT proliferation assay). These findings suggest that carbohydrate-based anti-adhesive candidates may provide potential leads for therapeutics for severe malaria.

Item Type: Article
Additional Information: This is the final published version of the article (version of record). It first appeared online via Public Library of Science at https://doi.org/10.1371/journal.pone.0186276 - please refer to any applicable terms of use of the publisher.
Uncontrolled Keywords: Antimalarials, Cell Adhesion, Cell Proliferation, Endothelial Cells, Erythrocytes, Glycosaminoglycans, Human Umbilical Vein Endothelial Cells, Humans, Malaria, Falciparum, Plasmodium falciparum, Protozoan Proteins
Subjects: Q Science > QR Microbiology
Divisions: Faculty of Natural Sciences > School of Life Sciences
Related URLs:
Depositing User: Symplectic
Date Deposited: 09 Nov 2017 14:31
Last Modified: 09 Nov 2017 14:33
URI: http://eprints.keele.ac.uk/id/eprint/4204

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