Dissertation
CAMPYLOBACTER JEJUNI MANIPULATES THE FOCAL COMPLEX TO INVADE EPITHELIAL CELLS AND INDUCE SECRETION OF INTERLEUKIN-8
Doctor of Philosophy (PhD), Washington State University
01/2014
Handle:
https://hdl.handle.net/2376/111806
Abstract
The focal complex is a set of signaling and structural proteins that govern cell attachment and motility. In epithelial cells focal complex proteins are required for regulating cell migration as well as pro-survival signaling. Several of the focal complex proteins are potent signaling molecules that activate signaling cascades regulating cytoskeletal rearrangements and gene expression necessary for these two functions. This dissertation is composed of two studies that examine the manner in which bacterial pathogens access and manipulate the focal complex signaling pathways to promote acute disease.
Campylobacter jejuni is a Gram-negative spiral shaped bacteria that is the leading cause of bacterial enteritis in the world. C. jejuni infection (campylobacteriosis) is characterized by blood and leukocytes in the stool of effected individuals, indicating bacterial invasion of the cells lining the intestine (epithelial cells). Campylobacteriosis is also accompanied by intense cramping, indicating an intense inflammatory response in the gut.
The first study focused on the role of focal complex signaling proteins during the entry of the bacterial pathogen Campylobacter jejuni into human epithelial cells. We show that C. jejuni manipulates cytoskeletal rearrangement components of the focal complex to cause human epithelial cells to engulf the pathogenic bacteria.
The second study examines the effect of bacterial interaction with the focal complex on the regulation of pro-inflammatory genes. We focus on the regulation of interleukin-8 (IL-8) expression and secretion, as it is one of the key proteins secreted by epithelial cells to recruit immune cells following bacterial infection. We show that the focal complex is required for activation of the signaling pathways leading to expression of IL-8 in human epithelial cells.
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Details
- Title
- CAMPYLOBACTER JEJUNI MANIPULATES THE FOCAL COMPLEX TO INVADE EPITHELIAL CELLS AND INDUCE SECRETION OF INTERLEUKIN-8
- Creators
- Tyson Eucker
- Contributors
- Michael E Konkel (Advisor)Mary Hunzicker-Dunn (Committee Member)Lisa Gloss (Committee Member)Scott A Minnich (Committee Member)
- Awarding Institution
- Washington State University
- Academic Unit
- Molecular Biosciences, School of
- Theses and Dissertations
- Doctor of Philosophy (PhD), Washington State University
- Number of pages
- 163
- Identifiers
- 99900581645001842
- Language
- English
- Resource Type
- Dissertation