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

Beckham, K. S.H. et al. (2014) The metabolic enzyme AdhE controls the virulence of Escherichia coli O157:H7. Molecular Microbiology, 93(1), pp. 199-211. (doi:10.1111/mmi.12651) (PMID:24846743) (PMCID:PMC4249723)

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Abstract

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.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Roe, Dr Andrew and Burgess, Dr Karl and Gawthorne, Ms Jayde and Burchmore, Dr Richard and Connolly, Dr James and Wang, Mr Dai and Beatson, Dr Scott and Douce, Dr Gillian and Smith, Dr Brian and Byron, Professor Olwyn
Authors: Beckham, K. S.H., Connolly, J. P.R., Ritchie, J. M., Wang, D., Gawthorne, J. A., Tahoun, A., Gally, D. L., Burgess, K., Burchmore, R. J., Smith, B. O., Beatson, S. A., Byron, O., Wolfe, A. J., Douce, G., and Roe, A. J.
College/School:College of Medical Veterinary and Life Sciences > Institute of Infection Immunity and Inflammation
College of Medical Veterinary and Life Sciences > School of Life Sciences
Journal Name:Molecular Microbiology
Publisher:Wiley-Blackwell Publishing Ltd
ISSN:0950-382X
ISSN (Online):1365-2958
Copyright Holders:Copyright © 2014 The Authors
First Published:First published in Molecular Microbiology 93(1):199-211
Publisher Policy:Reproduced under a Creative Commons License

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
526801Molecular Functions in DiseaseDarren MoncktonWellcome Trust (WELLCOME)089891/Z/09/ZRI MOLECULAR CELL & SYSTEMS BIOLOGY