Electronic Thesis and Dissertation Repository

Disruption of Insertion Sequence 200 (IS200) leads to a premature induction of the Cysteine regulon in Salmonella Typhimurium

Naomi-Jean Q. Scherba, The University of Western Ontario

Abstract

Salmonella Typhimurium is a leading contributor to non-typhoid diseases with complex regulatory networks that are key to understanding its pathogenicity and virulence. I explore the role of the sRNA IS200, where its deletion in Salmonellaleads to premature induction of the Cys regulon. The premature induction in ∆IS200 was validated through qRT-PCR and GFP transcriptional fusions and occurs at late exponential to early stationary phase. In addition, ∆IS200 leads to increased sensitivity to oxidative stress. The focus of this work has been to understand how ∆IS200 leads to premature Cys regulon induction, and I present three models: the futile import/export, the metabolic burden, and LrhA deprivation models. I conclude that the third model, which proposes a novel function for the global regulator LrhA, provides a promising direction for future research. Understanding this problem will help uncover how IS200 has integrated itself into the metabolic machinery of a medically important pathogen.