CHOLESTEROL STARVATION INDUCES DIFFERENTIATION OF THE INTESTINAL PARASITE GIARDIA-LAMBLIA

Giardia lamblia, like most human intestinal parasitic protozoa, sustai ns fundamental morphological and biochemical changes to survive outsid e the small intestine of its mammalian host by differentiating into an infective cyst. However, the stimulus that triggers this differentiat ion remains totally undefined. In this work, we demonstrate the induct ion of cyst formation in vitro when trophozoites are starved for chole sterol. Expression of cyst wall proteins was detected within encystati on-specific secretory vesicles 90 min after the cells were placed in l ipoprotein-deficient TYI-S-33 medium. Four cloned lines derived from t wo independent Giardia isolates were tested, and all formed cysts simi larly. Addition of cholesterol, low density or very low density lipopr oteins to the lipoprotein-deficient culture medium, inhibited the expr ession of cyst wall proteins, the generation of encystation-specific v esicles, and cyst wall biogenesis. In contrast, high density lipoprote ins, phospholipids, bile salts, or fatty acids had little or no effect . These results indicate that cholesterol starvation is necessary and sufficient for the stimulation of Giardia encystation in vitro and, li kely, in the intestine of mammalian hosts.