CHARACTERIZATION OF VIRULENCE-ASSOCIATED PROTEINS OF THE TYPE III SECRETION SYSTEMS IN ENTERIC PATHOGENS

Abstract

Enteric pathogens have a substantial impact on human health as they can cause outbreaks and severe disease outcomes. These pathogens employ many virulence strategies to evade host defenses and cause disease. While some virulence strategies have been carefully studied, other mechanisms remain largely uncharacterized. In addition, there are a number of putative virulence factors that have yet to be phenotypically or biochemically characterized. In order to facilitate the development of novel and effective treatment strategies for enteric pathogens, an understanding of how these putative virulence-associated proteins contribute to pathogenesis is required. In this work, the characterizations of two proteins implicated in the processes of motility and type III secretion are presented. The Escherichia coli O157:H7 protein Z0021 is found in an O-island unique to the most virulent serotypes of Shiga-toxin producing E. coli. Z0021 was found to encode for a repressor of motility that exerted its regulatory effect prior to the activation of class II promoters in the flagellar cascade. This work provided the first identification and characterization of a fimbrial operon-encoded motility repressor in E. coli O157:H7. The second protein, SsaN, from Salmonella enterica is a putative type III secretion system ATPase. This work examined the role of SsaN in virulence and effector secretion, and moreover provided insight into the mechanism by which SsaN binds to a chaperone to facilitate effector secretion. Together, these findings contribute to the understanding of the virulence strategies of two enteric pathogens that have had, and continue to have, significant impacts on human health worldwide.