Date of Award

2013

Degree Type

Thesis

Degree Name

Master of Science (MS)

Department

Microbiology and Immunology

Abstract

Clostridium difficile infection (CDI) is a major hospital-acquired diarrhea that can cause life-threatening complications such as pseudomembranous colitis. CDI is caused by colonization of host with C. difficile, a Gram positive, anaerobic bacterium known to produce toxins that cause disease. Normally, the gut microbiota protects the host from CDI, but disruption of the microbial composition through antibiotic treatment can leave one vulnerable for CDI. To date, no vaccines for preventing CDI are available.

In this study, the potential of antibodies directed against specific surface molecules of C. difficile to block bacterial adherence to host gut epithelial cells was studied, in hopes for developing a vaccine that could prevent colonization and disease. Antibodies against recombinant FliD (flagellar cap protein), HMW SLP (surface-associated protein), and Cwp84 (cysteine protease) were generated in rabbits and tested for their ability to reduce C. difficile adherence to Caco-2 BBE cells, a human colon-derived epithelial cell line. In this model, the antibodies against target molecules did not significantly decrease C. difficile adherence, although the target molecules had been found to be adhesins in the literature using other models. Thus, these data suggest that blocking of C. difficile adherence to epithelial cells using antibodies against adherence-associated surface molecules may be assay-dependent, highlighting a need to develop other models that can effectively simulate the in vivo conditions of CDI pathogenesis.

Creative Commons License

Creative Commons Attribution-Noncommercial-No Derivative Works 3.0 License
This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 3.0 License.

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