CHARACTERIZATION OF PHOSPHOGLYCAN-CONTAINING SECRETORY PRODUCTS OF LEISHMANIA

This article presents an overview on phosphoglycan-containing componen ts secreted by the insect and mammalian stages of several species of L eishmania, the causative agents of leishmaniasis in the Old and New Wo rld. Firstly, promastigotes of all three species considered, L. mexica na, L. donovani and L. major, shed lipophosphoglycan (LPG) into the cu lture medium possibly by release of micelles from the cell surface. Li ke the cell-associated LPG, culture supernatant LPG is amphiphilic and composed of a lysoalkylphosphatidylinositol-phosphosaccharide core co nnected to species-specific phosphosaccharide repeats and oligosacchar ide caps. Secondly, all three species release hydrophilic phosphoglyca n. Thirdly, all three species appear to secrete proteins covalently mo dified by phosphosaccharide repeats and oligosaccharide caps. In the c ase of promastigotes of L. mexicana, these components are organized as two filamentous polymers released from the flagellar pocket: the secr eted acid phosphatase (sAP) composed of a 100 kDa phosphoglycoprotein and a protein-containing high-molecular-weight-phosphoglycan (proteo-H MWPG) and fibrous networks likewise composed of phosphoglycan possibly linked to protein. Structural analyses and gene cloning suggest that the parasites can covalently modify protein regions rich in serine and threonine residues by the attachment of phosphosaccharide repeats cap ped by oligosaccharides. We propose that the networks formed in vitro correspond to fibrous material previously demonstrated in the digestiv e tract of infected sandflies. In the case of L. donovani, the sAP is also modified by phosphoglycans but contains neither proteo-HMWPG nor does it aggregate to filaments. Finally, L. mexicana amastigotes relea se proteo-HMWPG via the flagellar pocket into the parasitophorous vacu ole of infected macrophages. This material appears to be released into the tissue of the infected mammal upon rupture of infected macrophage s during lesion development. This secretory product may contribute to the pathology of lesion development.