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The metabolic enzyme AdhE controls the virulence of Escherichia coli O157: H7

Lookup NU author(s): Dr Kate BeckhamORCiD, Dr James ConnollyORCiD

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This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).


Abstract

Summary: Classical studies have focused on the role that individual regulators play in controlling virulence gene expression. An emerging theme, however, is that bacterial metabolism also plays a key role in this process. Our previous work identified a series of proteins that were implicated in the regulation of virulence. One of these proteins was AdhE, a bi-functional acetaldehyde-CoA dehydrogenase and alcohol dehydrogenase. Deletion of its gene (adhE) resulted in elevated levels of extracellular acetate and a stark pleiotropic phenotype: strong suppression of the Type Three Secretion System (T3SS) and overexpression of non-functional flagella. Correspondingly, the adhE mutant bound poorly to host cells and was unable to swim. Furthermore, the mutant was significantly less virulent than its parent when tested in vivo, which supports the hypothesis that attachment and motility are central to the colonization process. The molecular basis by which AdhE affects virulence gene regulation was found to be multifactorial, involving acetate-stimulated transcription of flagella expression and post-transcriptional regulation of the T3SS through Hfq. Our study reveals fascinating insights into the links between bacterial physiology, the expression of virulence genes, and the underlying molecular mechanism mechanisms by which these processes are regulated. © 2014 The Authors. Molecular Microbiology published by John Wiley & Sons Ltd.


Publication metadata

Author(s): Beckham KSH, Connolly JPR, Ritchie JM, Wang D, Gawthorne JA, Tahoun A, Gally DL, Burgess K, Burchmore RJ, Smith BO, Beatson SA, Byron O, Wolfe AJ, Douce GR, Roe AJ

Publication type: Article

Publication status: Published

Journal: Molecular Microbiology

Year: 2014

Volume: 93

Issue: 1

Pages: 199-211

Print publication date: 01/07/2014

Online publication date: 21/05/2014

Acceptance date: 17/05/2014

Date deposited: 23/09/2019

ISSN (print): 0950-382X

ISSN (electronic): 1365-2958

Publisher: Wiley-Blackwell

URL: https://doi.org/10.1111/mmi.12651

DOI: 10.1111/mmi.12651

PubMed id: 24846743


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Funding

Funder referenceFunder name
089891/Z/09/Z
R01 GM066130

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