Intra-species and stage-specific polymorphisms in lipophosphoglycan structure control Leishmania donovani-sand fly interactions

The Leishmania lipophosphoglycan conveys the ability for the parasites to a void destruction in diverse host environments. During its life cycle within the sand fly vector, the parasite differentiates from a dividing procyclic promastigote stage that avoids expulsion from the midgut by attaching to t he gut wall, to a nondividing metacyclic promastigote stage that is unable to attach to the midgut and migrates to the mouth parts for reinfection of a mammalian host. Lipophosphoglycan plays an integral role during this tran sition. Structurally, lipophosphoglycan is a multidomain glycoconjugate who se polymorphisms among species lie in the backbone Gal(beta 1,4)Man(alpha 1 )-PO4 repeating units and the oligosaccharide cap. We have characterized th e lipophosphoglycan from an Indian L. donovani isolate. Unlike East African isolates, which express unsubstituted repeats and a galactose- and mannose -terminating cap, procyclic lipophosphoglycan from the Indian isolate consi sts of beta 1,3-linked glucose residues that branch off the backbone repeat s (n similar to 17) and also terminate the cap. Of biological significance, metacyclic lipophosphoglycan lacks the glucose residues while doubling the number of repeats. The importance of these developmental modifications in lipophosphoglycan structure was determined using binding experiments to Phl ebotomus argentypes mid,outs. Procyclic promastigotes and procyclic LPG wer e able to bind to sand fly midguts in vitro whereas metacyclic parasites an d LPG lost this capacity. These results demonstrate that the Leishmania ada pts the synthesis of terminally exposed sugars of its LPG to manipulate par asite-sand fly interactions.