Enterococcus faecalis Metalloprotease Compromises Epithelial Barrier and Contributes to Intestinal Inflammation
Open accessAbstract
Background & aims Matrix metalloproteases (MMPs) mediate pathogenesis of chronic intestinal inflammation. We characterized the role of the gelatinase (GelE), a metalloprotease from Enterococcus faecalis, in the development of colitis in mice.Methods Germ-free, interleukin-10-deficient (IL-10(-/-)) mice were monoassociated with the colitogenic E faecalis strain OG1RF and isogenic, GelE-mutant strains. Barrier function was determined by measuring E-cadherin expression, transepithelial electrical resistance (TER), and translocation of permeability markers in colonic epithelial cells and colon segments from IL-10(-/-) and TNF(ΔARE/Wt) mice. GelE specificity was shown with the MMP inhibitor marimastat.Results Histologic analysis (score 0-4) of E faecalis monoassociated IL-10(-/-) mice revealed a significant reduction in colonic tissue inflammation in the absence of bacteria-derived GelE. We identified cleavage sites for GelE in the sequence of recombinant mouse E-cadherin, indicating that it might be degraded by GelE. Experiments with Ussing chambers and purified GelE revealed the loss of barrier function and extracellular E-cadherin in mice susceptible to intestinal inflammation (IL-10(-/-) and TNF(ΔARE/Wt) mice) before inflammation developed. Colonic epithelial cells had reduced TER and increased translocation of permeability markers after stimulation with GelE from OG1RF or strains of E faecalis isolated from patients with Crohn's disease and ulcerative colitis.Conclusions The metalloprotease GelE, produced by commensal strains of E faecalis, contributes to development of chronic intestinal inflammation in mice that are susceptible to intestinal inflammation (IL-10(-/-) and TNF(ΔARE/Wt) mice) by impairing epithelial barrier integrity.
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The metalloprotease GelE, produced by Enterococcus faecalis, degrades E-cadherin leading to loss of barrier function that is evident before inflammation in a mouse model of spontaneous colitis.
“The metalloprotease GelE, produced by Enterococcus faecalis, degrades E-cadherin leading to loss of barrier function that is evident before inflammation in a mouse model of spontaneous colitis.131”
From The emerging roles of bacterial proteases in intestinal diseases (2023) · cites this paper as [131]
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References 46 · Cited by 343
- Authors
- Steck, N., Hoffmann, M., Sava, I. G., Kim, S. C., Hahne, H., Tonkonogy, S. L., Mair, K., Krueger, D., Pruteanu, M., Shanahan, F., Vogelmann, R., Schemann, M., Kuster, B., Sartor, R. B., & Haller, D.
- Affiliations
- Technical University of Munich (DE)
- University of North Carolina at Chapel Hill (US)
- TUM Klinikum (DE)
- National University of Ireland (IE)
- Corresponding author
- Haller, Dirk
- ORCID
- Venue
- Gastroenterology
- Publisher
- Elsevier BV
- Published
- 2011-09
- Volume
- 141
- Issue
- 3
- Pages
- 959-971
- ISSN
- 0016-5085 (ISSN-L)
- OpenAlex
- W2104249477
- Cited by
- 343
- References
- 46
- Citations by year
- 2026: 31 · 2025: 38 · 2024: 26 · 2023: 27 · 2022: 26 · 2021: 30 · 2020: 19 · 2019: 22 · 2018: 20 · 2017: 18 · 2016: 10 · 2015: 17 · 2014: 20 · 2013: 12 · 2012: 21
- FWCI
- 11.77
- Type
- journal article
- Language
- en
- Open access
- green
- mediatum.ub.tum.de
- Licence
- Locations
- Gastroenterology (publishedVersion)
- PubMed (publishedVersion)
- mediaTUM – the media and publications repository of the Technical University Munich (Technical University Munich) (submittedVersion)
- mediaTUM – the media and publications repository of the Technical University Munich (Technical University Munich) (submittedVersion, other-oa)
- Funders
- European Commission
- Deutsche Forschungsgemeinschaft
- National Institutes of Health
- National Institute of Diabetes and Digestive and Kidney Diseases (R01DK053347)
- National Center for Research Resources (P40RR018603)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Inflammatory Bowel Disease
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Protease and Inhibitor Mechanisms
- Keywords
- Enterococcus faecalis, gelatinase, matrix metalloproteinases, intestinal epithelial barrier, colitis, intestinal inflammation, E-cadherin cleavage, transepithelial electrical resistance, commensal bacteria, IL-10 deficiency, TNF-deficient mice, Crohn's disease, ulcerative colitis, bacterial virulence factors
- MeSH terms
- Animals, Cell Membrane Permeability, Colitis, Disease Models, Animal, Intestinal Mucosa, Mice, Mutant Strains, Enterococcus faecalis, Tumor Necrosis Factor-alpha, CD4-Positive T-Lymphocytes, Cadherins, Interleukin-10, Gram-Positive Bacterial Infections, Gelatinases, Mice, Knockout, Metalloproteases, Mice
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