Giardia Cathepsins and Their Role in Intestinal Disease

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.

Name thesis:degree_name

Master of Science (MSc)

Discipline thesis:degree_discipline

Biological Sciences

Grantor dc:publisher.institution

Graduate Studies

Year dc:date.issued

2014

Author dc:creator

• Bhargava, Amol

Advisor dc:contributor.advisor

• Buret, Andre

• Parasitology

Statement dc:rights

• University of Calgary graduate students retain copyright ownership and moral rights for their thesis. You may use this material in any way that is permitted by the Copyright Act or through licensing that has been assigned to the document. For uses that are not allowable under copyright legislation or licensing, you are required to seek permission.

Language dc:language.iso

eng

DOI

http://dx.doi.org/10.11575/PRISM/26304

OAI identifier oai:identifier

oai:ucalgary.scholaris.ca:11023/1675