Distinct intra-species virulence mechanisms regulated by a conserved transcription factor

Connolly, J. P.R., O'Boyle, N., Turner, N., Browning, D. F. and Roe, A. J. (2019) Distinct intra-species virulence mechanisms regulated by a conserved transcription factor. Proceedings of the National Academy of Sciences of the United States of America, 116(39), pp. 19695-19704. (doi: 10.1073/pnas.1903461116) (PMID:31501343) (PMCID:PMC6765310)

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Abstract

Bacterial pathogens emerge by adapting mechanisms of virulence, differentiating them from their nonpathogenic progenitor. Virulence factors are often encoded on accessory genomic elements not part of the core genome and therefore must be integrated into the regulatory architecture of the cell. Here, we show that a highly conserved transcription factor in Escherichia coli has been relieved of a common purpose and adapted to regulate virulence pleiotropically in 2 distinct genetic backgrounds. This leads to enhanced virulence of both intestinal enterohemorrhagic E. coli and extraintestinal uropathogenic E. coli by exclusive mechanisms. These findings challenge the assumption that conserved transcription factors regulate common pathways maintained within a species and suggest that transcriptional repurposing creates new primary roles on an individual basis.

Item Type:Articles
Additional Information:This work was supported by Biotechnology and Biological Sciences Research Council (BBSRC) funding (BB/M029646/1 and BB/ R006539/1) awarded to A.J.R., and a Wellcome Trust Institutional Strategic Support Fund (204820/Z/16/Z) awarded to J.P.R.C.
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Turner, Natasha and Connolly, Dr James and Roe, Professor Andrew and O Boyle, Dr Nicky
Authors: Connolly, J. P.R., O'Boyle, N., Turner, N., Browning, D. F., and Roe, A. J.
College/School:College of Medical Veterinary and Life Sciences
College of Medical Veterinary and Life Sciences > School of Infection & Immunity
Journal Name:Proceedings of the National Academy of Sciences of the United States of America
Publisher:National Academy of Sciences
ISSN:0027-8424
ISSN (Online):1091-6490
Published Online:09 September 2019
Copyright Holders:Copyright © 2019 The Authors
First Published:First published in Proceedings of the National Academy of Sciences of the United States of America 116(39): 19695-19704
Publisher Policy:Reproduced under a Creative Commons License

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
691101Where and Why: The Influence of Host Metabolism on Bacterial Niche SpecificityAndrew RoeBiotechnology and Biological Sciences Research Council (BBSRC)BB/M029646/1III - BACTERIOLOGY
3002800The Role of Dietary D-serine in Health and DiseaseAndrew RoeBiotechnology and Biological Sciences Research Council (BBSRC)BB/R006539/1III - Bacteriology
742591Institutional Strategic Support Fund (2016)Anna DominiczakWellcome Trust (WELLCOTR)204820/Z/16/ZRI CARDIOVASCULAR & MEDICAL SCIENCES