Intra-Species and Stage-Specific Polymorphisms in Lipophosphoglycan Structure Control Leishmania donovani−Sand Fly Interactions

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Abstract
The Leishmania lipophosphoglycan conveys the ability for the parasites to avoid 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 the 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 transition. Structurally, lipophosphoglycan is a multidomain glycoconjugate whose polymorphisms among species lie in the backbone Gal(β1,4)Man(α1)-PO4 repeating units and the oligosaccharide cap. We have characterized the 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 consists of β1,3-linked glucose residues that branch off the backbone repeats (n ∼ 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 Phlebotomus argentipes midguts. Procyclic promastigotes and procyclic LPG were able to bind to sand fly midguts in vitro whereas metacyclic parasites and LPG lost this capacity. These results demonstrate that the Leishmania adapts the synthesis of terminally exposed sugars of its LPG to manipulate parasite−sand fly interactions.
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