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.
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Cover Image
Cover Image
The image represents a simplified ‘open’ cell of the gram-positive bacterium Streptomyces coelicolor and selected components of its zinc metabolism. The zinc sensor protein – zinc uptake regulator (Zur) – is shown in metallic blue in the middle, bound to DNA (green) where it works as a transcriptional repressor when zinc levels are adequate. The Zur-regulated high-affinity zinc uptake system ZnuABC is shown in purple. Synthesis of the secreted zincophore coelibactin is also Zur-regulated. Zinc ions are shown as silver balls surrounding the cell, and bound to Zur; for details see pages 983–1001.
The image has been created by Alevtina Mikhaylina with the help of Claudia A. Blindauer and David J. Scanlan.
The role of heparan sulfate in host macrophage infection by Leishmania species Available to Purchase
Marissa L. Maciej-Hulme, Mark A. Skidmore, Helen P. Price; The role of heparan sulfate in host macrophage infection by Leishmania species. Biochem Soc Trans 20 August 2018; 46 (4): 789–796. doi: https://doi.org/10.1042/BST20170398
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