STRUCTURE OF LEISHMANIA LIPOPHOSPHOGLYCAN - INTER-SPECIFIC AND INTRA-SPECIFIC POLYMORPHISM IN OLD-WORLD SPECIES

The most abundant surface macromolecule on the promastigote stage of l eishmanial parasites is a polymorphic lipophosphoglycan (LPG). We have elucidated the structures of two new LPGs, from Leishmania tropica (L RC-L36) and L. aethiopica (LRC-L495), and investigated the nature of i ntra-specific polymorphism in the previously characterized LPG of L. m ajor (LRC-L456 and -L580). These molecules contain a phosphoglycan cha in, made up of repeating PO4-6Gal beta 1-4Man units and a conserved he xaglycosyl-phosphatidylinositol membrane anchor. Extensive polymorphis m occurs in the extent to which the LPG repeat units are substituted w ith different glycan side chains. The L. tropica LPG is the most compl ex LPG characterized to date, as most of the repeat units are substitu ted with more than 19 different glycan side chains. All of these side chains, including the novel major glycans, Arap beta 1-3Glc beta 1- an d +/- Arap beta 1-2Glc beta 1-4[+/- Arap beta 1-2]Glc beta 1-, are lin ked to the C-3 position of the backbone disaccharide galactose. In con trast, the L. aethiopica LPG repeat units are partially substituted (3 5%) with single alpha-mannose residues that are linked, unusually, to the C-2 position of the mannose in the backbone disaccharide. Polymorp hism is also evident in the spectrum of alpha-mannose-containing oligo saccharides that cap the non-reducing terminus of the phosphoglycan ch ains of these LPGs. Finally, analysis of the L. major LPGs showed that , while some strains contain LPGs which are highly substituted with si de chains of beta Gal, Gal beta 1-3Gal beta 1- and Arap beta 1-2Gal be ta 1-3Gal beta 1- the LPGs of other strains (i.e L. major LRC-L456) ar e essentially unsubstituted. Recent studies have shown that the LPG si de chains and cap structures can mediate promastigote attachment to a number of different receptors along the midgut of the sandfly vector. The possible significance of LPG polymorphism on the ability of these parasites to infect a number of different sandfly vectors is discussed .