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Cefoperazone-treated Mouse Model of Clinically-relevant Clostridium difficile Strain R20291
Published on: December 10, 2016
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Human Clostridium difficile infection: altered mucus production and composition
Melinda A Engevik1, Mary Beth Yacyshyn2, Kristen A Engevik1
1Department of Molecular and Cellular Physiology, University of Cincinnati College of Medicine, Cincinnati, Ohio;
Summary
Clostridium difficile infection (CDI) alters intestinal mucus, decreasing MUC2 and changing oligosaccharides. This mucus composition facilitates C. difficile binding and colonization, suggesting new therapeutic targets.
Area of Science:
- Gastroenterology
- Microbiology
- Immunology
Background:
- Antibiotic-induced diarrhea is primarily caused by Clostridium difficile (C. difficile).
- C. difficile infection (CDI) hospitalizations have significantly increased, necessitating a deeper understanding of its colonization mechanisms.
- Intestinal mucus plays a crucial role in host-bacterial interactions and gut health.
Purpose of the Study:
- To investigate changes in mucus production and composition in patients with CDI compared to healthy individuals.
- To elucidate the role of mucus alterations in C. difficile colonization and infection.
Main Methods:
- Analysis of MUC1 and MUC2 mucin expression and mucus oligosaccharide composition in healthy and CDI patients.
- In vitro experiments assessing C. difficile growth on various sugars.
- Human intestinal organoid (HIO) models to study C. difficile interaction with host mucus.
- Binding assays comparing C. difficile adherence to mucus from healthy and CDI subjects.
Main Results:
- CDI patients showed reduced MUC2 levels and altered mucus oligosaccharide profiles (decreased GalNAc, increased GlcNAc, and increased terminal galactose).
- C. difficile can metabolize key mucus sugars for growth.
- C. difficile alone reduced MUC2 production in HIOs but did not alter oligosaccharide composition.
- C. difficile exhibited preferential binding to mucus from CDI patients.
Conclusions:
- Altered intestinal mucus composition in CDI patients, particularly changes in MUC2 and specific oligosaccharides, may promote C. difficile colonization.
- The increased presence of terminal galactose residues in CDI mucus is significant, as it acts as a receptor for C. difficile toxin A.
- These findings offer insights into C. difficile pathogenesis and suggest potential targets for novel therapeutic interventions.
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