Giardia Cathepsins and Their Role in Intestinal Disease

Abstract

Giardia duodenalis, a non-invasive protozoan parasite of the upper small intestine of mammals, including humans, closely associates with intestinal epithelial cells. The pathophysiology of giardiasis includes intestinal barrier dysfunction and cytoskeletal injury; however, the mechanisms or parasitic factors involved remain unclear. The Giardia genome contains genes for cathepsin-like cysteine proteases; however, their roles are unknown. Using an in vitro model for studying host-parasite interactions, we illustrated that G. duodenalis trophozoites contain and release cathepsin B/L-like cysteine proteases. While cathepsin-like cysteine proteases are not involved in the tight junctional disruption caused by G. duodenalis, such proteases cleaved and disrupted cytoskeletal villin. This disruption of villin was sustained over time, at least in part, by host MLCK. Overall, this study establishes a reliable model for studying roles of parasitic cysteine proteases during host-parasite interactions. Further understanding of these proteases may pave the way for therapeutic development.