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  1. Article ; Online: The role of mucin

    Fekete, Elena / Buret, Andre G

    American journal of physiology. Gastrointestinal and liver physiology

    2023  Volume 324, Issue 6, Page(s) G452–G465

    Abstract: ... ...

    Abstract Mucin
    MeSH term(s) Humans ; Mucins/metabolism ; Intestinal Mucosa/metabolism ; Dysbiosis ; Microbiota ; Host-Pathogen Interactions ; Homeostasis ; Polysaccharides/chemistry ; Mucin-2/metabolism
    Chemical Substances Mucins ; Polysaccharides ; Mucin-2
    Language English
    Publishing date 2023-04-18
    Publishing country United States
    Document type Journal Article ; Review ; Research Support, Non-U.S. Gov't
    ZDB-ID 603840-2
    ISSN 1522-1547 ; 0193-1857
    ISSN (online) 1522-1547
    ISSN 0193-1857
    DOI 10.1152/ajpgi.00261.2022
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  2. Article: Giardia Cysteine Proteases: The Teeth behind the Smile

    Allain, Thibault / Fekete, Elena / Buret, Andre G

    Trends in parasitology. 2019 Aug., v. 35, no. 8

    2019  

    Abstract: Giardia duodenalis is one of the most prevalent human enteropathogens and a major cause of diarrheal disease worldwide. Cysteine proteases (CPs) have been identified as major virulence factors in protozoan parasites, playing important roles in disease ... ...

    Abstract Giardia duodenalis is one of the most prevalent human enteropathogens and a major cause of diarrheal disease worldwide. Cysteine proteases (CPs) have been identified as major virulence factors in protozoan parasites, playing important roles in disease pathogenesis and in parasitic life cycles. G. duodenalis exhibits high proteolytic activity, and CPs play significant roles in giardiasis. Giardia CPs are directly involved in intestinal epithelial junctional complex disruption, intestinal epithelial cell apoptosis, and degradation of host immune factors, including chemokines and immunoglobulins. Giardia CPs have also been implicated in mucus depletion and microbiota dysbiosis induced by the parasite. This review discusses the most recent advances in characterization of Giardia Assemblage A and B CPs, including cathepsin B (catB)-like proteases.
    Keywords Giardia lamblia ; apoptosis ; cathepsin B ; chemokines ; diarrhea ; dysbiosis ; enteropathogens ; giardiasis ; humans ; immunoglobulins ; intestinal mucosa ; microorganisms ; mucus ; parasites ; pathogenesis ; proteolysis ; teeth ; virulence
    Language English
    Dates of publication 2019-08
    Size p. 636-648.
    Publishing place Elsevier Ltd
    Document type Article
    ZDB-ID 2036227-4
    ISSN 1471-5007 ; 1471-4922
    ISSN (online) 1471-5007
    ISSN 1471-4922
    DOI 10.1016/j.pt.2019.06.003
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  3. Article ; Online: Giardia Cysteine Proteases: The Teeth behind the Smile.

    Allain, Thibault / Fekete, Elena / Buret, Andre G

    Trends in parasitology

    2019  Volume 35, Issue 8, Page(s) 636–648

    Abstract: Giardia duodenalis is one of the most prevalent human enteropathogens and a major cause of diarrheal disease worldwide. Cysteine proteases (CPs) have been identified as major virulence factors in protozoan parasites, playing important roles in disease ... ...

    Abstract Giardia duodenalis is one of the most prevalent human enteropathogens and a major cause of diarrheal disease worldwide. Cysteine proteases (CPs) have been identified as major virulence factors in protozoan parasites, playing important roles in disease pathogenesis and in parasitic life cycles. G. duodenalis exhibits high proteolytic activity, and CPs play significant roles in giardiasis. Giardia CPs are directly involved in intestinal epithelial junctional complex disruption, intestinal epithelial cell apoptosis, and degradation of host immune factors, including chemokines and immunoglobulins. Giardia CPs have also been implicated in mucus depletion and microbiota dysbiosis induced by the parasite. This review discusses the most recent advances in characterization of Giardia Assemblage A and B CPs, including cathepsin B (catB)-like proteases.
    MeSH term(s) Cysteine Proteases/metabolism ; Giardia/enzymology ; Giardiasis/enzymology ; Giardiasis/parasitology ; Humans ; Protozoan Proteins/metabolism ; Research/trends ; Virulence Factors/metabolism
    Chemical Substances Protozoan Proteins ; Virulence Factors ; Cysteine Proteases (EC 3.4.-)
    Language English
    Publishing date 2019-07-03
    Publishing country England
    Document type Journal Article ; Review
    ZDB-ID 2036227-4
    ISSN 1471-5007 ; 1471-4922
    ISSN (online) 1471-5007
    ISSN 1471-4922
    DOI 10.1016/j.pt.2019.06.003
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  4. Article: Giardia

    Fekete, Elena / Allain, Thibault / Siddiq, Affan / Sosnowski, Olivia / Buret, Andre G

    Frontiers in microbiology

    2021  Volume 11, Page(s) 618106

    Abstract: Alteration of the intestinal microbiome by enteropathogens is commonly associated with gastrointestinal diseases and disorders and has far-reaching consequences for overall health. Significant advances have been made in understanding the role of ... ...

    Abstract Alteration of the intestinal microbiome by enteropathogens is commonly associated with gastrointestinal diseases and disorders and has far-reaching consequences for overall health. Significant advances have been made in understanding the role of microbial dysbiosis during intestinal infections, including infection with the protozoan parasite
    Language English
    Publishing date 2021-01-12
    Publishing country Switzerland
    Document type Journal Article ; Review
    ZDB-ID 2587354-4
    ISSN 1664-302X
    ISSN 1664-302X
    DOI 10.3389/fmicb.2020.618106
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  5. Article ; Online: Giardia duodenalis cysteine proteases cleave proteinase-activated receptor-2 to regulate intestinal goblet cell mucin gene expression.

    Fekete, Elena / Allain, Thibault / Amat, Christina B / Mihara, Koichiro / Saifeddine, Mahmoud / Hollenberg, Morley D / Chadee, Kris / Buret, Andre G

    International journal for parasitology

    2022  Volume 52, Issue 5, Page(s) 285–292

    Abstract: Giardia duodenalis cysteine proteases have been identified as key virulence factors and have been implicated in alterations to intestinal goblet cell activity and mucus production during Giardia infection. The present findings demonstrate a novel ... ...

    Abstract Giardia duodenalis cysteine proteases have been identified as key virulence factors and have been implicated in alterations to intestinal goblet cell activity and mucus production during Giardia infection. The present findings demonstrate a novel mechanism by which Giardia cysteine proteases modulate goblet cell activity via cleavage and activation of protease-activated receptor 2. Giardia duodenalis (assemblage A) increased MUC2 mucin gene expression in human colonic epithelial cells in a manner dependent upon both protease-activated receptor 2 activation and Giardia cysteine protease activity. Protease-activated receptor 2 cleavage within the N-terminal activation domain by Giardia proteases was confirmed using a nano-luciferase tagged recombinant protease-activated receptor 2. In keeping with these observations, the synthetic protease-activated receptor 2-activating peptide 2fLIGRLO-amide increased Muc2 gene expression in a time-dependent manner. Calcium chelation and inhibition of the ERK1/2 mitogen activated protein kinase pathway inhibited Muc2 upregulation during Giardia infection, consistent with canonical protease-activated receptor 2 signaling pathways. Giardia cysteine proteases cleaved both recombinant protease-activated receptor 1 and protease-activated receptor 2 within their extracellular activation domains with isolate-dependent efficiency that correlated with the production of cysteine protease activity. Protease-activated receptors represent a novel target for Giardia cysteine proteases, and these findings demonstrate that protease-activated receptor 2 can regulate mucin gene expression in intestinal goblet cells.
    MeSH term(s) Cysteine Proteases/genetics ; Cysteine Proteases/metabolism ; Gene Expression ; Giardia lamblia/enzymology ; Giardia lamblia/genetics ; Goblet Cells/metabolism ; Humans ; Mucins/metabolism ; Receptor, PAR-2/genetics ; Receptor, PAR-2/metabolism
    Chemical Substances F2RL1 protein, human ; Mucins ; Receptor, PAR-2 ; Cysteine Proteases (EC 3.4.-)
    Language English
    Publishing date 2022-01-22
    Publishing country England
    Document type Journal Article
    ZDB-ID 120518-3
    ISSN 1879-0135 ; 0020-7519
    ISSN (online) 1879-0135
    ISSN 0020-7519
    DOI 10.1016/j.ijpara.2021.11.011
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  6. Article: Giardia duodenalis cysteine proteases cleave proteinase-activated receptor-2 to regulate intestinal goblet cell mucin gene expression

    Fekete, Elena / Allain, Thibault / Amat, Christina B. / Mihara, Koichiro / Saifeddine, Mahmoud / Hollenberg, Morley D. / Chadee, Kris / Buret, Andre G.

    International journal for parasitology. 2021 Nov. 11,

    2021  

    Abstract: Giardia duodenalis cysteine proteases have been identified as key virulence factors and have been implicated in alterations to intestinal goblet cell activity and mucus production during Giardia infection. The present findings demonstrate a novel ... ...

    Abstract Giardia duodenalis cysteine proteases have been identified as key virulence factors and have been implicated in alterations to intestinal goblet cell activity and mucus production during Giardia infection. The present findings demonstrate a novel mechanism by which Giardia cysteine proteases modulate goblet cell activity via cleavage and activation of protease-activated receptor 2. Giardia duodenalis (assemblage A) increased MUC2 mucin gene expression in human colonic epithelial cells in a manner dependent upon both protease-activated receptor 2 activation and Giardia cysteine protease activity. Protease-activated receptor 2 cleavage within the N-terminal activation domain by Giardia proteases was confirmed using a nano-luciferase tagged recombinant protease-activated receptor 2. In keeping with these observations, the synthetic protease-activated receptor 2-activating peptide 2fLIGRLO-amide increased Muc2 gene expression in a time-dependent manner. Calcium chelation and inhibition of the ERK1/2 mitogen activated protein kinase pathway inhibited Muc2 upregulation during Giardia infection, consistent with canonical protease-activated receptor 2 signaling pathways. Giardia cysteine proteases cleaved both recombinant protease-activated receptor 1 and protease-activated receptor 2 within their extracellular activation domains with isolate-dependent efficiency that correlated with the production of cysteine protease activity. Protease-activated receptors represent a novel target for Giardia cysteine proteases, and these findings demonstrate that protease-activated receptor 2 can regulate mucin gene expression in intestinal goblet cells.
    Keywords Giardia lamblia ; calcium ; chelation ; cysteine proteinases ; enzyme activity ; gene expression ; humans ; intestines ; mitogen-activated protein kinase ; mucins ; mucus ; parasitology ; peptides ; virulence
    Language English
    Dates of publication 2021-1111
    Publishing place Elsevier Ltd
    Document type Article
    Note Pre-press version
    ZDB-ID 120518-3
    ISSN 1879-0135 ; 0020-7519
    ISSN (online) 1879-0135
    ISSN 0020-7519
    DOI 10.1016/j.ijpara.2021.11.011
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  7. Article ; Online: High-fat diet increases the severity of Giardia infection in association with low-grade inflammation and gut microbiota dysbiosis.

    Allain, Thibault / Fekete, Elena / Sosnowski, Olivia / Desmonts de Lamache, Dimitri / Motta, Jean-Paul / Leger, Dezirae / Feener, Troy / Reimer, Raylene A / Buret, André G

    Scientific reports

    2021  Volume 11, Issue 1, Page(s) 18842

    Abstract: Exogenous factors that may influence the pathophysiology of Giardia infection remain incompletely understood. We have investigated the role of dietary fat in the pathogenesis of Giardia infection. Male 3 to 4-week-old C57BL/6 mice were fed either a low ... ...

    Abstract Exogenous factors that may influence the pathophysiology of Giardia infection remain incompletely understood. We have investigated the role of dietary fat in the pathogenesis of Giardia infection. Male 3 to 4-week-old C57BL/6 mice were fed either a low fat (LF) or a high fat (HF) diet for 12 days and challenged with G. duodenalis. In infected animals, the trophozoite burden was higher in HF + Giardia mice compared to the LF + Giardia group at day 7 post infection. Fatty acids exerted direct pro-growth effects on Giardia trophozoites. Analysis of disease parameters showed that HF + Giardia mice exhibited more mucosal infiltration by inflammatory cells, decreased villus/crypt ratios, goblet cell hyperplasia, mucus disruption, increased gut motility, and elevated fecal water content compared with LF + Giardia. HF diet-dependent exacerbation of Giardia-induced goblet cell hyperplasia was associated with elevated Atoh1 and Muc2 gene expression. Gut microbiota analysis revealed that the HF diet alone induces a taxonomic shift. HF + Giardia mice exhibited microbiota dysbiosis characterized by an increase of Firmicutes and a decrease of Bacteroidetes and significant changes in α- and β-diversity metrics. Taken together, the findings suggest that a HF diet exacerbates the outcome of Giardia infection. The data demonstrate that elevated dietary fat represents an important exogenous factor promoting the pathophysiology of giardiasis.
    MeSH term(s) Animals ; Cytokines/blood ; Diet, Fat-Restricted/adverse effects ; Diet, High-Fat/adverse effects ; Dysbiosis/etiology ; Fatty Acids/adverse effects ; Gastrointestinal Microbiome/physiology ; Giardia ; Giardiasis/etiology ; Inflammation/etiology ; Male ; Mice ; Mice, Inbred C57BL ; Tight Junction Proteins/antagonists & inhibitors ; Trophozoites
    Chemical Substances Cytokines ; Fatty Acids ; Tight Junction Proteins
    Language English
    Publishing date 2021-09-22
    Publishing country England
    Document type Journal Article
    ZDB-ID 2615211-3
    ISSN 2045-2322 ; 2045-2322
    ISSN (online) 2045-2322
    ISSN 2045-2322
    DOI 10.1038/s41598-021-98262-8
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  8. Article ; Online: Cysteine Protease-Dependent Mucous Disruptions and Differential Mucin Gene Expression in Giardia duodenalis Infection.

    Amat, Christina B / Motta, Jean-Paul / Fekete, Elena / Moreau, France / Chadee, Kris / Buret, Andre G

    The American journal of pathology

    2017  Volume 187, Issue 11, Page(s) 2486–2498

    Abstract: The intestinal mucous layer provides a critical host defense against pathogen exposure and epithelial injury, yet little is known about how enteropathogens may circumvent this physiologic barrier. Giardia duodenalis is a small intestinal parasite ... ...

    Abstract The intestinal mucous layer provides a critical host defense against pathogen exposure and epithelial injury, yet little is known about how enteropathogens may circumvent this physiologic barrier. Giardia duodenalis is a small intestinal parasite responsible for diarrheal disease and chronic postinfectious illness. This study reveals a complex interaction at the surface of epithelial cells, between G. duodenalis and the intestinal mucous layer. Here, we reveal mechanisms whereby G. duodenalis evades and disrupts the first line of host defense by degrading human mucin-2 (MUC2), depleting mucin stores and inducing differential gene expression in the mouse small and large intestines. Human colonic biopsy specimens exposed to G. duodenalis were depleted of mucus, and in vivo mice infected with G. duodenalis had a thinner mucous layer and demonstrated differential Muc2 and Muc5ac mucin gene expression. Infection in Muc2
    Language English
    Publishing date 2017-11
    Publishing country United States
    Document type Journal Article
    ZDB-ID 2943-9
    ISSN 1525-2191 ; 0002-9440
    ISSN (online) 1525-2191
    ISSN 0002-9440
    DOI 10.1016/j.ajpath.2017.07.009
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