Giardia duodenalis Surface Cysteine Proteases Induce Cleavage of the Intestinal Epithelial Cytoskeletal Protein Villin via Myosin Light Chain Kinase

PloS One
Amol BhargavaAndre G Buret

Abstract

Giardia duodenalis infections are among the most common causes of waterborne diarrhoeal disease worldwide. At the height of infection, G. duodenalis trophozoites induce multiple pathophysiological processes within intestinal epithelial cells that contribute to the development of diarrhoeal disease. To date, our understanding of pathophysiological processes in giardiasis remains incompletely understood. The present study reveals a previously unappreciated role for G. duodenalis cathepsin cysteine proteases in intestinal epithelial pathophysiological processes that occur during giardiasis. Experiments first established that Giardia trophozoites indeed produce cathepsin B and L in strain-dependent fashion. Co-incubation of G. duodenalis with human enterocytes enhanced cathepsin production by Assemblage A (NF and S2 isolates) trophozoites, but not when epithelial cells were exposed to Assemblage B (GSM isolate) trophozoites. Direct contact between G. duodenalis parasites and human intestinal epithelial monolayers resulted in the degradation and redistribution of the intestinal epithelial cytoskeletal protein villin; these effects were abolished when parasite cathepsin cysteine proteases were inhibited. Interestingly, inhibition of ...Continue Reading

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Citations

Feb 27, 2017·International Journal for Parasitology·Jennifer K BeattyAndre G Buret
Sep 7, 2018·PLoS Neglected Tropical Diseases·Camila H Coelho, Steven M Singer
Aug 2, 2016·Current Opinion in Infectious Diseases·Luther A Bartelt, James A Platts-Mills
Sep 8, 2020·The FEBS Journal·Deepani Darshika Fernando, Katja Fischer
Oct 6, 2020·Frontiers in Genetics·Dimitra PeirasmakiStaffan G Svärd
Apr 30, 2017·Tissue Barriers·Thibault AllainAndré G Buret
Oct 12, 2017·Frontiers in Cellular and Infection Microbiology·Martin R KraftToni Aebischer
Jul 8, 2019·Trends in Parasitology·Thibault AllainAndre G Buret
Jan 30, 2021·Frontiers in Microbiology·Elena FeketeAndre G Buret
Aug 22, 2017·The American Journal of Pathology·Christina B AmatAndre G Buret
Aug 12, 2021·Clinical Microbiology Reviews·Rodney D Adam

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Methods Mentioned

BETA
IECs
IEC
PCR
electrophoresis

Software Mentioned

ImageJ
Bioedit
Graphpad Prism
BLAST
SeqScape

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