The role of phosphoglycans in Leishmania-sand fly interactions

Leishmania promastigotes synthesize an abundance of phosphoglycans, either attached to the cell surface through phosphatidylinositol anchors (lipophos phoglycan, LPG) or secreted as protein-containing glycoconjugates. These ph osphoglycans are thought to promote the survival of the parasite within bot h its vertebrate and invertebrate hosts. The relative contributions of diff erent phosphoglycan-containing molecules in Leishmania-sand fly interaction s were tested by using mutants specifically deficient in either total phosp hoglycans or LPG alone. Leishmania donovani promastigotes deficient in both LPC and protein-linked phosphoglycans because of loss of LPG2 (encoding th e Co(gi GDP-Man transporter) failed to survive the hydrolytic environment w ithin the early blood-fed midgut, In contrast, L. donovani and Leishmania m ajor mutants deficient solely in LPC expression because of loss of LPG 1 (i nvolved in biosynthesis of the core oligosaccharide LPG domain) had only a slight reduction in the survival and growth of promastigotes within the ear ly blood-fed midgut. The ability of the LPG1-deficient promastigotes to per sist in the midgut after blood meal excretion was completely lost, and this defect was correlated with their inability to bind to midgut epithelial ce lls in vitro. For both mutants, when phosphoglycan expression was restored to wild-type levels by reintroduction of LPG1 or LPG2 (as appropriate), the n the wild-type phenotype was also restored. We conclude, first, that LPG i s not essential for survival in the early blood-fed midgut but. along with other secreted phosphoglycan-containing glycoconjugates, can protect promas tigotes from the digestive enzymes in the gut and, second, that LPG is requ ired to mediate midgut attachment and to maintain infection in the fly duri ng excretion of the digested blood meal.