377 Sphingolipids: Are They Critical for Encystation?

Friday, November 6, 2009: 9:30 AM
Angus (Camino Real Hotel)
Siddhartha Das, Ph.D. , University of Texas at El Paso, Department of Biological Sciences, El Paso, TX
 Sphingolipids regulate various cellular functions such as differentiation, apoptosis, and signaling in mammalian cells. Recent results suggest that ceramide and other sphingolipids are also important for encystation and cyst production by intestinal protozoa, Giardia and Entamoeba. The genomic analyses indicated that while Giardia contains fewer sphingolipid metabolic genes, Entamoeba has almost all of the genes except dihydroceramide synthase and dihydroceramide desaturase. This difference, as far as sphingolipid metabolism is concerned, is interesting because both organisms are phylogenetically basal and were proposed earlier not to synthesize the majority of lipids and fatty acids de novo. Functional analyses indicated that 3-keto-sphinganine (a product of serine-palmitoyltransferase enzyme) regulates ceramide endocytosis, and that glucosylceramide (catalyzed by glucosylceramide transferase 1) induces cyst production in both Giardia and Entamoeba. In this presentation, I will discuss how sphingolipid genes and enzymes regulate the growth and encystation of these two pathogens. An attempt will also been made to examine the possibility of using sphingolipid metabolic pathways as targets for developing novel therapeutics against Giardia and Entamoeba that are reported to infect over one billion people annually, worldwide.