INHIBITION OF GLYCOSYLPHOSPHATIDYLINOSITOL BIOSYNTHESIS IN LEISHMANIA-MEXICANA BY MANNOSAMINE

In several Leishmania species, glycosylated inositol phospholipids exi st as free lipids, as membrane protein anchors, and as the membrane-bi nding moieties of the lipophosphoglycans. Both the glycolipid-anchored cell surface metalloproteinase, gp63, and the lipophosphoglycans have been proposed to be involved in cell invasion. Moreover, the lipophos phoglycans have been implicated in the survival of Leishmania in the p arasitophorous vacuole of the host macrophage. In this report we show that mannosamine effectively inhibits the biosynthesis of both free gl ycosylated inositol phospholipids and the lipophosphoglycans of Leishm ania mexicana. [H-3]Mannosamine is incorporated into glycosylated inos itol phospholipids, but not significantly into lipophosphoglycans when added as a radiochemical tracer at a subinhibitory concentration. The reversible inhibitory effect of mannosamine may be useful for studyin g precursor/product relationships during the biosynthesis of free glyc osylated inositol phospholipids, glycolipid anchors, and the lipophosp hoglycans. The implications of these data for the mode of action of ma nnosamine are discussed.