Thermoregulation of two Pseudomonas aeruginosa virulence factors Open Access

Prezioso, Samantha (Fall 2018)

Permanent URL: https://etd.library.emory.edu/concern/etds/gf06g358n?locale=en
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Abstract

Pseudomonas aeruginosa is a gram-negative environmental bacteria that can, at times, act as an opportunistic pathogen. A strategy utilized by bacteria to ensure appropriate expression of genes is to sense and respond to changes in local temperature. Most research on temperature regulation focuses on the up-regulation or induction of gene expression upon a shift from 22-25°C to 37°C. However, not all virulence factors are regulated in this pattern. An important but understudied aspect of temperature regulation involves virulence factors that are expressed at higher levels at lower temperatures.

     The work presented here contributes to filling this gap in knowledge by examining the thermoregulatory mechanisms of two P. aeruginosa virulence factors: EftM and PrpL. EftM is a methyltransferase that catalyzes a post-translational modification on elongation factor-tu, which, when it is surface exposed, enhances bacterial adhesion to human epithelial cells. Studies of EftM have revealed two independent layers of thermoregulation for this protein. These independent mechanisms are mRNA transcription initiation and post-translational protein instability, making EftM a dual thermoregulated methyltransferase. PrpL is a secreted protease that releases iron and aids in tissue invasion. This work uncovers that prpL mRNA is thermoregulated at the level of transcription initiation, mediated by the hns-like MvaT and MvaU. Further, thermoregulation is independent of two other known regulatory mechanisms of prpL: quorum sensing and iron dependence.

           Ultimately these studies further our knowledge of the mechanisms regulating expression of these two virulence factors, which leads to a more complete understanding of P. aeruginosa pathogenesis. Further, this work lays the foundation for uncovering a larger network of genes thermoregulated in this unique pattern.

Table of Contents

Abstract

Table of Contents

List of Tables and Figures

Chapter I: Introduction…………………………………………………………………1

Chapter II: Elfamycins: Inhibitors of Elongation Factor-Tu………………………..27

Chapter III: Trimethylation of Elongation Factor-Tu by the Dual Thermoregulated Methyltransferase EftM Does Not Impact Its Canonical Function in Translation……………………………………………………………………………...61

Chapter IV: Phenotypic Studies of EftM…………………………………………...107

Chapter V: Investigation into the Mechanism of Transcriptional Thermoregulation for the Pseudomonas aeruginosa Virulence Factor PrpL………………………..166

Chapter VI: Future Directions for Studies of EftM and PrpL…………………….201

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