GP49, AN INVARIANT GPI-ANCHORED ANTIGEN OF GIARDIA-LAMBLIA

Giardia lamblia is a primitive protozoan and a major cause of waterbor ne enteric disease throughout tropical and temperate zones. The abilit y to grow the infective trophozoites in culture as well as the discove ry of the method of in vitro encystation made it possible to study the biology of this primitive protozoan and to characterize the surface a ntigens. Giardia trophozoites are exposed to high concentrations of fa tty acids in the human small intestine. This raises the possibility th at intestinal fatty acids may become incorporated into Giardia. Theref ore, we determined the pattern of fatty acylation of Giardia surface m olecules. By metabolic labeling with radiolabeled fatty acids we ident ified a single glycosylphosphatidylinositol (GPI)-anchored surface pro tein in Giardia, GP49 differs from the cysteinerich variable surface a ntigens described previously. The presence of a GPI anchor in GP49 was supported by the metabolic incorporation of [C-14]-ethanolamine, [H-3 ]-myoinositol and fatty acids into the protein. This was confirmed by chemical and enzymatic cleavage experiments. Most interestingly, GP49 was found to be present in different isolates of Giardia and thus can be considered as an invariant surface antigen. Although the biological function of GP49 is not known,recently we have found that intact and soluble GP49 altered the electrolyte fluxes which regulate fluid secre tion in the cultured human intestinal epithelial cell line, T84. These studies indicate that the GPI-anchored invariant antigen of Giardia m ay play an important role in the pathophysiology of giardiasis.