Degradation of the extracellular matrix components by bacterial-derived metalloproteases: Implications for inflammatory bowel diseases
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BACKGROUND: Proteolytic degradation of the extracellular matrix, a feature of mucosal homeostasis and tissue renewal, also contributes to the complications of intestinal inflammation. Whether this proteolytic activity is entirely host-derived, or, in part, produced by the gut microbiota, is unknown. METHODS: We screened the bacterial colonies for gelatinolytic activity from fecal samples of 20 healthy controls, 23 patients with ulcerative colitis, and 18 with Crohn's disease (CD). In addition, the genes encoding metalloproteases were detected by conventional or real-time polymerase chain reaction (PCR). RESULTS: Gelatinolytic activity was found in approximately one-quarter of samples regardless of the presence of inflammation and without any attempt to enhance the sensitivity of the culture-based screen. This was associated with a diversity of bacteria, particularly in CD, but was predominantly linked with Clostridium perfringens. Culture supernatants from C. perfringens degraded gelatin, azocoll, type I collagen, and basement membrane type IV collagen, but different isolates varied in the degree of proteolytic activity. Results were confirmed by detection of the C. perfringens colA gene (encoding collagenase) in fecal DNA, again regardless of the presence or absence of inflammation. However, the biologic significance and potential implications of microbial-derived proteolytic activity were confirmed by reduced transepithelial resistance (TER) after exposure of rat distal colon to culture supernatants of C. perfringens in Ussing chambers. CONCLUSIONS: The study shows that microbial-derived proteolytic activity has the capacity to contribute to mucosal homeostasis and may participate in the pathogenesis of inflammatory bowel disease.
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Proteases from different microorganisms exhibit strong proteolytic mucinase activity.
“Proteases from different microorganisms also exhibit strong proteolytic mucinase activity.124”
From The emerging roles of bacterial proteases in intestinal diseases (2023) · cites this paper as [124]
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- Authors
- Pruteanu, M., Hyland, N. P., Clarke, D. J., Kiely, B., & Shanahan, F.
- Affiliations
- National University of Ireland (IE)
- Alimentary Health (Ireland) (IE)
- Venue
- Inflammatory Bowel Diseases
- Publisher
- Oxford University Press (OUP)
- Published
- 2011-05
- Volume
- 17
- Issue
- 5
- Pages
- 1189-1200
- ISSN
- 1078-0998 (ISSN-L)
- OpenAlex
- W2073360547
- Cited by
- 67
- References
- 64
- Citations by year
- 2025: 3 · 2024: 3 · 2023: 2 · 2022: 6 · 2021: 6 · 2019: 8 · 2017: 7 · 2016: 4 · 2015: 4 · 2014: 5 · 2013: 6 · 2012: 9
- FWCI
- 3.41
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Inflammatory Bowel Diseases (publishedVersion)
- PubMed (publishedVersion)
- Zenodo (CERN European Organization for Nuclear Research) (submittedVersion, other-oa)
- Funders
- European Commission (202020)
- Science Foundation Ireland
- 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
- extracellular matrix degradation
- MeSH terms
- Adult, Animals, Bacterial Proteins, Basement Membrane, Microbial Collagenase, Clostridium perfringens, Colitis, Ulcerative, Crohn Disease, Extracellular Matrix, Feces, Humans, Metalloendopeptidases, Microbiological Techniques, Middle Aged, Staphylococcus epidermidis, Polymerase Chain Reaction, Collagen Type IV, Gastrointestinal Tract, Metalloproteases, Rats, Metagenome, In Vitro Techniques
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