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CC BY V4.0, Open Access
Thesis
Campylobacter jejuni trigger signaling through host cell focal adhesions to inhibit cell motility and impede wound repair
Washington State University
Master of Science (MS), Washington State University
01/2021
DOI:
https://doi.org/10.7273/000001848
Handle:
https://hdl.handle.net/2376/120848
Abstract
The pathogenic bacteria Campylobacter jejuni is a leading cause of gastroenteritis worldwide. A combination of short-term symptoms including nausea, abdominal cramps, fever, and diarrhea with blood and leukocytes as well as possible long-term consequences including intestinal dysregulation and autoimmune induced paralysis make understanding C. jejuni pathogenesis of importance. C. jejuni causes sickness by invading epithelial cells lining the intestine, resulting in villous blunting and damage. Previous research has shown that C. jejuni invasion requires proteins in host cell focal adhesions, dynamic complexes connecting intracellular actin bundles to the extracellular matrix. To further understand cell signaling events that occur during bacterial invasion, we investigated the dynamics of focal adhesion structure, signaling, and function in infected cells. Epithelial cells were found to be less motile during C. jejuni infection in single cell motility assays as well collective cell migration assays that mimic intestinal villi wound healing. The mechanism of these changes was determined to be due to C. jejuni altering the focal adhesion composition and size. The focal adhesion footprint size increased and a corresponding decrease in cytosolic focal adhesion protein was observed. In addition, the major focal adhesion protein paxillin was phosphorylated and had an increased localization to focal adhesions. In agreement with these findings, the rate of focal adhesion turnover was reduced, and cells became more adherent to the substrate. To assess bacterial mechanism, we investigated the dependence of well-studied C. jejuni virulence factors in changing the focal adhesion. Both the adhesins CadF and FlpA and the flagella / protein secretion were required for paxillin phosphorylation, motility, and wound healing. These results support a model in which C. jejuni manipulates the focal adhesion with virulence attributes to change cell behavior. These findings demonstrate that C. jejuni can modify the focal adhesion throughout invasion and provide a starting place for understanding observed in vivo intestinal damage.
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Details
- Title
- Campylobacter jejuni trigger signaling through host cell focal adhesions to inhibit cell motility and impede wound repair
- Creators
- Courtney M Klappenbach
- Contributors
- Michael E Konkel (Advisor)Alan Goodman (Committee Member)Philip Mixter (Committee Member)Gary Wayman (Committee Member)
- Awarding Institution
- Washington State University
- Academic Unit
- Molecular Biosciences, School of
- Theses and Dissertations
- Master of Science (MS), Washington State University
- Publisher
- Washington State University
- Number of pages
- 121
- Identifiers
- 99900606549101842
- Language
- English
- Resource Type
- Thesis