Discussion

Leishmaniasis is caused by infection with the protozoan parasite Leishmania and is endemic in 98 countries, with approximately 2 million new cases annually. With resistant strains emerging to the few drugs available, more detailed information about mechanisms of infection is required to fuel new approaches to therapeutics. The role of carbohydrates in Leishmania infection remain largely unexplored. Previous work in the field has shown that the glycosaminoglycan, heparan sulphate (HS), can modify the adhesion of various Leishmania species to cells, possibly mediating parasite pathogenicity. HS is a linear polysaccharide comprised of repeating backbone structure of glucuronic acid and N-acetylglucosamine disaccharides. During synthesis, the backbone is modified by a plethora of enzymes, resulting in fine chemical patterning of the chain. This primary structure is thought to bind target biomolecules and mediate their function. Compositional analysis of human macrophage HS shows a large quantity of 2-O-sulphation of the chain. The identification of specific HS epitopes on macrophages will enable targeted therapies to be developed to reduce parasitic invasion of macrophage cells. Indeed, using a novel small soluble inhibitor of HS, the expression of HS at the cell surface can be reduced and limits the parasite burden, thus potentiating an alternative therapeutic approach for Leishmaniasis.