Date of Award

Spring 2013

Abstract

Stx-2 is a major contributor to the pathogenesis of Escherichia coli 0157:H7. Prior reports suggest that Stx-2 increases necrosis and apoptosis of a variety of host cells including those of endothelial origin as well as immune cells such as neutrophils (156). However, the role Stx-2 plays in delayed apoptosis of neutrophils is not fully understood given that previous studies have shown conflicting results (118, 51). The process of apoptosis is mediated by the Bcl-2 protein family (2, 46, 226). The purpose of this research was to define the molecular mechanisms of Stx-2 and Bcl-2 protein family interactions. These studies examined the binding of Stx-2 to select Bcl-2 family proteins, and outlined the effects that Stx-2 and a newly generated mutant of Stx-2 have on neutrophil apoptosis and necrosis rates as well as on caspase-8 and caspase-9 activation. Stx-2 did not bind to the select Bcl-2 family proteins examined nor did it consistently show decreased apoptosis rates in neutrophils. The mechanisms behind Stx-2-induced neutrophil apoptosis potentially involved the endoplasmic reticulum (ER) stress response and/or interactions with other Bcl-2 family members such as Bak at the mitochondrial membrane therefore inducing mitochondrial membrane permeabilization (MMP) and its downstream effects.

Document Type

Dissertation

First Advisor

Frank Rodgers

Department or Program

Microbiology

Degree Name

Doctor of Philosophy

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