DEVELOPMENTAL BIOLOGY OF LEISHMANIA PROMASTIGOTES

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During growth within the sand fly and within axenic culture, Leishmania promastigotes undergo differentiation from a dividing non-infective stage to a resting infective or metacyclic stage which is uniquely adapted for life in the vertebrate. The culture conditions which promote differentiation of parasites to an infective stage have now been optimized for various strains. This development is accompanied by a substantial modification of the surface lipophosphoglycan (LPG) which is the major surface glycoconjugate of these cells. The developmental modifications include an elongation of the molecule due to a 2-3 fold increase in the number of phosphorylated oligosaccharated units expressed, and a change in the composition of some of these units. In the case of L. major and L. donovani the structural polymorphism is expressed as a loss of terminal galactose residues on the LPG. Related structural changes have now been confirmed for L. amazonensis and L. infantum. The substitution or capping of terminally exposed sugars with other sugar residues was shown to be the molecular mechnism underlying the attachment and release of promastigotes from midgut epithelial cells during their development in the fly. The specific oligosaccharide units which mediate the binding have now been identified. The species specificity of these terminal sugars appears to influence the species specificity of vectorial capacity observed in nature. LPG has been successfully used to probe for the lectin like receptors in the sand fly gut. In related studies, it was found that the presence of anti-LPG antibodies within an infective bloodmeal inhibited the development of transmissible infections within the sand fly midgut. This inhibition was only apparent when the bloodmeal also contained anti-leishmanial antibodies present in chronic infection sera.