ArticlePloS one2015
Giardia duodenalis Surface Cysteine Proteases Induce Cleavage of the Intestinal Epithelial Cytoskeletal Protein Villin via Myosin Light Chain Kinase.
Article in PloS one, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.
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33 citing papers in PubMed, 66 citations in OpenAlex.
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- Giardia duodenalis stabilizes HIF-1α and induces glycolytic alterations in intestinal epithelial cells.Scientific reports · 2025Article
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- Current Understanding ofCurrent tropical medicine reports · 2024Article
- A thermo-resistant and RNase-sensitive cargo fromJournal of extracellular biology · 2023Article
- Extracellular Cysteine Proteases of Key Intestinal Protozoan Pathogens-Factors Linked to Virulence and Pathogenicity.International journal of molecular sciences · 2023Review
- Tandem mass tag-based quantitative proteomics analyses of a chicken-original virulent and its attenuatedFrontiers in veterinary science · 2023Article
- Application of Proteomics to the Study of the Therapeutics and Pathogenicity ofDiagnostics (Basel, Switzerland) · 2022Review
- The Cysteine Protease Giardipain-1 fromInternational journal of molecular sciences · 2022Article
- Mucosal Defense AgainstFrontiers in immunology · 2022Review
- High-fat diet increases the severity of Giardia infection in association with low-grade inflammation and gut microbiota dysbiosis.Scientific reports · 2021Article
- Age andMicroorganisms · 2021Article
- Article
- Giardia duodenalis Virulence - "To Be, or Not To Be".Current tropical medicine reports · 2021Review
- Harmonization of Protocols for Multi-Species Organoid Platforms to Study the Intestinal Biology ofFrontiers in cellular and infection microbiology · 2020Article
- Review
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
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 parasite proteases did not prevent degradation of the intestinal tight junction-associated protein zonula occludens 1 (ZO-1), suggesting that G. duodenalis induces multiple pathophysiological processes within intestinal epithelial cells. Finally, this study demonstrates that G. duodenalis-mediated disruption of villin is, at least, in part dependent on activation of myosin light chain kinase (MLCK). Taken together, this study indicates a novel role for parasite cathepsin cysteine proteases in the pathophysiology of G. duodenalis infections.
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