Date of Award

Spring 2013

Project Type

Dissertation

Program or Major

Microbiology

Degree Name

Doctor of Philosophy

First Advisor

Frank Rodgers

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.

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