Maciej-Hulme, ML, Skidmore, MA and Price, HP ORCID: 0000-0003-1537-4390 (2018) The role of heparan sulfate in host macrophage infection by Leishmania species. Biochemical Society Transactions, 46. pp. 789-796. ISSN 1470-8752

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Abstract

The leishmaniases are a group of neglected tropical diseases caused by parasites from the Leishmania genus. More than 20 Leishmania species are responsible for human disease, causing a broad spectrum of symptoms ranging from cutaneous lesions to a fatal visceral infection. There is no single safe and effective approach to treat these diseases and resistance to current anti-leishmanial drugs is emerging. New drug targets need to be identified and validated to generate novel treatments. Host heparan sulfates (HSs) are abundant, heterogeneous polysaccharides displayed on proteoglycans that bind various ligands, including cell surface proteins expressed on Leishmania promastigote and amastigote parasites. The fine chemical structure of HS is formed by a plethora of specific enzymes during biosynthesis, with various positions (N-, 2-O-, 6-O- and 3-O-) on the carbon sugar backbone modified with sulfate groups. Post-biosynthesis mechanisms can further modify the sulfation pattern or size of the polysaccharide, altering ligand affinity to moderate biological functions. Chemically modified heparins used to mimic the heterogeneous nature of HS influence the affinity of different Leishmania species, demonstrating the importance of specific HS chemical sequences in parasite interaction. However, the endogenous structures of host HSs that might interact with Leishmania parasites during host invasion have not been elucidated, nor has the role of HSs in host-parasite biology. Decoding the structure of HSs on target host cells will increase understanding of HS/parasite interactions in leishmaniasis, potentiating identification of new opportunities for the development of novel treatments.

Item Type: Article
Additional Information: This is the accepted author manuscript (AAM). The final published version (version of record) is available online via Portland Press at http://doi.org/10.1042/BST20170398 - please refer to any applicable terms of use of the publisher.
Uncontrolled Keywords: Leishmania, drug discovery and design, heparan sulfate, host–pathogen interactions, parasitology, proteoglycan
Subjects: Q Science > QH Natural history
Divisions: Faculty of Natural Sciences > School of Life Sciences
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Depositing User: Symplectic
Date Deposited: 02 Aug 2018 12:36
Last Modified: 10 Sep 2018 14:48
URI: http://eprints.keele.ac.uk/id/eprint/5193

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