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

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 regulatio...

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Autores principales: Beckham, Katherine S H, Connolly, James P R, Ritchie, Jennifer M, Wang, Dai, Gawthorne, Jayde A, Tahoun, Amin, Gally, David L, Burgess, Karl, Burchmore, Richard J, Smith, Brian O, Beatson, Scott A, Byron, Olwyn, Wolfe, Alan J, Douce, Gillian R, Roe, Andrew J
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BlackWell Publishing Ltd 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4249723/
https://www.ncbi.nlm.nih.gov/pubmed/24846743
http://dx.doi.org/10.1111/mmi.12651
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author Beckham, Katherine S H
Connolly, James P R
Ritchie, Jennifer M
Wang, Dai
Gawthorne, Jayde A
Tahoun, Amin
Gally, David L
Burgess, Karl
Burchmore, Richard J
Smith, Brian O
Beatson, Scott A
Byron, Olwyn
Wolfe, Alan J
Douce, Gillian R
Roe, Andrew J
author_facet Beckham, Katherine S H
Connolly, James P R
Ritchie, Jennifer M
Wang, Dai
Gawthorne, Jayde A
Tahoun, Amin
Gally, David L
Burgess, Karl
Burchmore, Richard J
Smith, Brian O
Beatson, Scott A
Byron, Olwyn
Wolfe, Alan J
Douce, Gillian R
Roe, Andrew J
author_sort Beckham, Katherine S H
collection PubMed
description 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.
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spelling pubmed-42497232015-01-26 The metabolic enzyme AdhE controls the virulence of Escherichia coli O157:H7 Beckham, Katherine S H Connolly, James P R Ritchie, Jennifer M Wang, Dai Gawthorne, Jayde A Tahoun, Amin Gally, David L Burgess, Karl Burchmore, Richard J Smith, Brian O Beatson, Scott A Byron, Olwyn Wolfe, Alan J Douce, Gillian R Roe, Andrew J Mol Microbiol Research Articles 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. BlackWell Publishing Ltd 2014-07 2014-06-09 /pmc/articles/PMC4249723/ /pubmed/24846743 http://dx.doi.org/10.1111/mmi.12651 Text en © 2014 The Authors. Molecular Microbiology published by John Wiley & Sons Ltd. http://creativecommons.org/licenses/by/3.0/ This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Articles
Beckham, Katherine S H
Connolly, James P R
Ritchie, Jennifer M
Wang, Dai
Gawthorne, Jayde A
Tahoun, Amin
Gally, David L
Burgess, Karl
Burchmore, Richard J
Smith, Brian O
Beatson, Scott A
Byron, Olwyn
Wolfe, Alan J
Douce, Gillian R
Roe, Andrew J
The metabolic enzyme AdhE controls the virulence of Escherichia coli O157:H7
title The metabolic enzyme AdhE controls the virulence of Escherichia coli O157:H7
title_full The metabolic enzyme AdhE controls the virulence of Escherichia coli O157:H7
title_fullStr The metabolic enzyme AdhE controls the virulence of Escherichia coli O157:H7
title_full_unstemmed The metabolic enzyme AdhE controls the virulence of Escherichia coli O157:H7
title_short The metabolic enzyme AdhE controls the virulence of Escherichia coli O157:H7
title_sort metabolic enzyme adhe controls the virulence of escherichia coli o157:h7
topic Research Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4249723/
https://www.ncbi.nlm.nih.gov/pubmed/24846743
http://dx.doi.org/10.1111/mmi.12651
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