KILLING OF GIARDIA-LAMBLIA BY CRYPTDINS AND CATIONIC NEUTROPHIL PEPTIDES

Antimicrobial polypeptides such as the defensins kill a wide range of organisms, including bacteria, fungi, viruses, and tumor cells. Becaus e of the recent finding that intestinal defensins, also known as crypt dins, are synthesized by the Paneth cells of the small intestinal cryp ts and released into the lumen, we asked whether defensins and other s mall cationic antimicrobial peptides could kill the trophozoites of Gi ardia lamblia, which colonize the small intestine. Four mouse cryptdin s, two neutrophil defensins (HNP-1 [human] and NP-2 [rabbit]), and the unique tryptophan-rich bovine neutrophil polypeptide indolicidin each had some antigiardial activity against trophozoites in vitro. Cryptdi ns 2 and 3, indolicidin, and NP-2 each reduced viability by more than 3 log units in 2 h, and killing by all peptides was dose and time depe ndent. Exposure of trophozoites to peptides frequently resulted in cel l aggregation and dramatic changes in morphology. The mechanism of bin ding and lysis appeared to involve charge interactions, since 150 mM N aCl as well as millimolar levels of Ca2+ and Mg2+ inhibited killing by most of the peptides. Our studies show that G. lamblia is sensitive t o defensins and indolicidin and suggest that these small polypeptides could play a role in nonimmune host defenses.