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Regulation of enteropathogenic Escherichia coli envelope protein expression by the Cpx response and small RNAs Open Access

Descriptions

Other title
Subject/Keyword
Cpx envelope stress response
enteropathogenic Escherichia coli
small RNAs
Hfq
bundle-forming pilus
Type of item
Thesis
Degree grantor
University of Alberta
Author or creator
Vogt, Stefanie L.
Supervisor and department
Raivio, Tracy (Biological Sciences)
Examining committee member and department
Owttrim, George (Biological Sciences)
Raivio, Tracy (Biological Sciences)
Szymanski, Christine (Biological Sciences)
Mulvey, Matthew (University of Utah)
Pukatzki, Stefan (Medical Microbiology and Immunology)
Department
Department of Biological Sciences
Specialization
Microbiology & Biotechnology
Date accepted
2013-09-24T09:28:52Z
Graduation date
2013-11
Degree
Doctor of Philosophy
Degree level
Doctoral
Abstract
Gram-negative bacteria are characterized by their complex cell envelope, which consists of the inner membrane, outer membrane, and intervening periplasmic space. Envelope-localized proteins play a critical role in many interactions of a bacterium with its environment, including uptake of nutrients, extrusion of waste, adhesion to surfaces, and motility. As such, regulation of envelope protein expression is crucial to the survival of Gram-negative organisms such as Escherichia coli. Two regulatory systems involved in controlling envelope protein expression are the Cpx envelope stress response and small non-coding RNAs (sRNAs). The Cpx response is believed to sense misfolding of inner membrane and periplasmic proteins; in response, Cpx increases the transcription of a suite of genes encoding envelope-localized protein folding and degrading factors. sRNAs, with assistance from the RNA chaperone protein Hfq, base-pair with target mRNAs to modulate their rate of translation and/or stability. The first goal of this thesis was to examine the regulatory effects of the Cpx response and sRNAs upon the expression of the bundle-forming pilus (BFP), an envelope-localized protein complex that mediates initial interaction of enteropathogenic E. coli (EPEC) with host cells. We found that the Cpx response affects BFP expression at multiple levels. Activation of the Cpx response represses transcription of the bfp gene cluster and prevents BFP expression, while inactivation of the Cpx response diminishes BFP expression at the post-translational level, as a result of decreased expression of periplasmic protein folding factors. The RNA chaperone Hfq also represses transcription of the bfp genes by destabilizing the perA transcript, which encodes the major regulator of bfp transcription. A second goal of this work was to characterize the interactions between the Cpx response and sRNAs. I demonstrated that the Cpx response regulates the expression of four sRNA-encoding genes. Conversely, Hfq and sRNAs also affect activity of the Cpx response, as deletion of hfq in EPEC activates the Cpx pathway, while overexpression of the sRNA RprA diminishes Cpx activity. These results deepen our understanding of how regulatory systems attune envelope protein expression to environmental and physiological conditions, thereby contributing to the pathogenesis of EPEC and related organisms.
Language
English
DOI
doi:10.7939/R35D8NR5Q
Rights
Permission is hereby granted to the University of Alberta Libraries to reproduce single copies of this thesis and to lend or sell such copies for private, scholarly or scientific research purposes only. Where the thesis is converted to, or otherwise made available in digital form, the University of Alberta will advise potential users of the thesis of these terms. The author reserves all other publication and other rights in association with the copyright in the thesis and, except as herein before provided, neither the thesis nor any substantial portion thereof may be printed or otherwise reproduced in any material form whatsoever without the author's prior written permission.
Citation for previous publication
Vogt, S.L. and T.L. Raivio. (2012) Just scratching the surface: an expanding view of the Cpx envelope stress response. FEMS Microbiology Letters 326(1):2-11.Vogt, S.L., A.Z. Nevesinjac, R.M. Humphries, M.S. Donnenberg, G.D. Armstrong, and T.L. Raivio. (2010) Molecular Microbiology 76(5):1095-1110.

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File title: Thesis
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