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Probing Clostridium difficile infection in complex human gut cellular models
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Anonye, Blessing O., Hassall, Jack, Patient, Jamie, Detamornrat, Usanee, Aladdad, Afnan M., Schüller, Stephanie, Rose, Felicity R. A. J. and Unnikrishnan, Meera (2019) Probing Clostridium difficile infection in complex human gut cellular models. Frontiers in Microbiology, 10 . 879. doi:10.3389/fmicb.2019.00879 ISSN 1664-302X.
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WRAP-probing-clostridium-difficile-infection-complex-human-gut-Unnikrishnan-2019.pdf - Published Version - Requires a PDF viewer. Available under License Creative Commons Attribution 4.0. Download (4080Kb) | Preview |
Official URL: http://dx.doi.org/10.3389/fmicb.2019.00879
Abstract
Interactions of anaerobic gut bacteria, such as Clostridium difficile, with the intestinal mucosa have been poorly studied due to challenges in culturing anaerobes with the oxygen-requiring gut epithelium. Although gut colonization by C. difficile is a key determinant of disease outcome, precise mechanisms of mucosal attachment and spread remain unclear. Here, using human gut epithelial monolayers co-cultured within dual environment chambers, we demonstrate that C. difficile adhesion to gut epithelial cells is accompanied by a gradual increase in bacterial numbers. Prolonged infection causes redistribution of actin and loss of epithelial integrity, accompanied by production of C. difficile spores, toxins, and bacterial filaments. This system was used to examine C. difficile interactions with the commensal Bacteroides dorei, and interestingly, C. difficile growth is significantly reduced in the presence of B. dorei. Subsequently, we have developed novel models containing a myofibroblast layer, in addition to the epithelium, grown on polycarbonate or three-dimensional (3D) electrospun scaffolds. In these more complex models, C. difficile adheres more efficiently to epithelial cells, as compared to the single epithelial monolayers, leading to a quicker destruction of the epithelium. Our study describes new controlled environment human gut models that enable host–anaerobe and pathogen–commensal interaction studies in vitro.
| Item Type: | Journal Article | ||||||
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| Divisions: | Faculty of Science, Engineering and Medicine > Medicine > Warwick Medical School > Biomedical Sciences Faculty of Science, Engineering and Medicine > Science > Life Sciences (2010- ) Faculty of Science, Engineering and Medicine > Medicine > Warwick Medical School > Biomedical Sciences > Microbiology & Infection Faculty of Science, Engineering and Medicine > Medicine > Warwick Medical School |
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| Journal or Publication Title: | Frontiers in Microbiology | ||||||
| Publisher: | Frontiers Research Foundation | ||||||
| ISSN: | 1664-302X | ||||||
| Official Date: | 30 April 2019 | ||||||
| Dates: |
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| Volume: | 10 | ||||||
| Article Number: | 879 | ||||||
| DOI: | 10.3389/fmicb.2019.00879 | ||||||
| Status: | Peer Reviewed | ||||||
| Publication Status: | Published | ||||||
| Access rights to Published version: | Open Access (Creative Commons) | ||||||
| Date of first compliant deposit: | 20 September 2019 | ||||||
| Date of first compliant Open Access: | 20 September 2019 |
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