The role of heparan sulfate in host macrophage infection by Leishmania species

• Published in: Biochemical Society transactions Vol. 46; no. 4; p. 789
• Main Authors: Maciej-Hulme, Marissa L, Skidmore, Mark A, Price, Helen P
• Format: Journal Article
• Language: English
• Published: England 20.08.2018
• Subjects: Animals; Antiprotozoal Agents - therapeutic use; Cell Adhesion Molecules - metabolism; Heparan Sulfate Proteoglycans - biosynthesis; Heparan Sulfate Proteoglycans - metabolism; Heparin - metabolism; Heparitin Sulfate - physiology; Host-Parasite Interactions; Humans; Leishmania - metabolism; Leishmania - pathogenicity; Leishmaniasis - drug therapy; Macrophages - parasitology; Protein Binding; Protozoan Proteins - metabolism; drug discovery and design; heparan sulfate; host–pathogen interactions; Leishmania; parasitology; proteoglycan
• ISSN: 1470-8752
• DOI: 10.1042/BST20170398

The leishmaniases are a group of neglected tropical diseases caused by parasites from the genus. More than 20 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 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 species, demonstrating the importance of specific HS chemical sequences in parasite interaction. However, the endogenous structures of host HSs that might interact with 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.