Dissertation
Fundamental mechanisms of Campylobacter jejuni pathogenesis: Analysis of the host inflammatory response and fibronectin adherence
Washington State University
Doctor of Philosophy (PhD), Washington State University
05/2010
DOI:
https://doi.org/10.7273/000006187
Abstract
Campylobacter jejuni is the most frequent bacterial cause of gastroenteritis in the world. Acute disease is associated with invasion of host epithelial cells and inflammation of the intestinal epithelium. C. jejuni virulence factors participate in motility, adherence, invasion, protein secretion, and intracellular survival. In contrast with humans, C. jejuni is a commensal organism in chickens. Indeed, C. jejuni infection is often a consequence of consuming foods contaminated with undercooked poultry. This dissertation contains a review of C. jejuni pathogenesis and protein secretion followed by two studies investigating C. jejuni virulence factors. The first study assessed the impact of innate immunity on the development of acute disease in a susceptible host. C. jejuni invaded human epithelial cells efficiently, whereas invasion of chicken epithelial cells was minimal. Expression of the chicken IL-8 orthologs was significantly less than the expression of human IL-8 in response to C. jejuni infection. These findings revealed that host cell invasion and activation of the host inflammatory response characterize the pathogenic relationship of C. jejuni with humans, but not the commensal relationship of C. jejuni with chickens. The second study investigated C. jejuni adherence to fibronectin (Fn), a process critical for C. jejuni host colonization and invasion of host cells. C. jejuni synthesizes two Fn-binding proteins - FlpA and CadF. The CadF Fn-binding domain was determined previously to be 134FRLS137. FlpA harbors three domains resembling Fn type 3 repeats: D1, D2, and D3. ELISAs were conducted to identify the FlpA Fn-binding domain. Fn adherence to FlpA-D2 was dosedependent and saturable, indicating the interaction was specific, whereas Fn adherence to D1 and D3 was nonspecific. The FlpA Fn-binding domain was localized further using overlapping synthetic peptides spanning the FlpA-D2 amino acids sequence. Maximal Fn-binding was localized to 158PHPDFRV164. Finally, it was determined that FlpA bound to the gelatin-binding domain of Fn. This characterization of the interactions between FlpA and Fn contributes to our understanding of how adherence to Fn contributes to C. jejuni pathogenesis. Studies are in progress to determine the impact of FlpA adherence to on CadF, and to understand how FlpA may contribute to host cell invasion.
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Details
- Title
- Fundamental mechanisms of Campylobacter jejuni pathogenesis
- Creators
- Charles L. Larson
- Contributors
- Michael E. Konkel (Chair)Lisa M Gloss (Committee Member)MICHAEL L. KAHN (Committee Member) - Washington State University, Institute of Biological ChemistryScott Arthur Minnich (Committee Member) - Washington State University, School of Food Science
- Awarding Institution
- Washington State University
- Academic Unit
- School of Molecular Biosciences
- Theses and Dissertations
- Doctor of Philosophy (PhD), Washington State University
- Publisher
- Washington State University
- Number of pages
- 184
- Identifiers
- 99901055128101842
- Language
- English
- Resource Type
- Dissertation