Genomic plasticity of pathogenic Escherichia coli mediates D-serine tolerance via multiple adaptive mechanisms

O'Boyle, N., Connolly, J. P.R., Tucker, N. P. and Roe, A. J. (2020) Genomic plasticity of pathogenic Escherichia coli mediates D-serine tolerance via multiple adaptive mechanisms. Proceedings of the National Academy of Sciences of the United States of America, 117(36), pp. 22484-22493. (doi: 10.1073/pnas.2004977117) (PMID:32848072) (PMCID:PMC7486766)

[img]
Preview
Text
221634.pdf - Published Version
Available under License Creative Commons Attribution.

2MB
[img] Text
221634.pdf - Published Version
Available under License Creative Commons Attribution.

2MB

Abstract

The molecular environment of the host can have profound effects on the behavior of resident bacterial species. We recently established how the sensing and response of enterohemorrhagic Escherichia coli (EHEC) to D-serine (D-Ser) resulted in down-regulation of type 3 secretion system-dependent colonization, thereby avoiding unfavorable environments abundant in this toxic metabolite. However, this model ignores a key determinant of the success of bacterial pathogens, adaptive evolution. In this study, we have explored the adaptation of EHEC to D-Ser and its consequences for pathogenesis. We rapidly isolated multiple, independent, EHEC mutants whose growth was no longer compromised in the presence of D-Ser. Through a combination of whole-genome sequencing and transcriptomics, we showed that tolerance could be attributed to disruption of one of two D-Ser transporters and/or activation of a previously nonfunctional D-Ser deaminase. While the implication of cytoplasmic transport in D-Ser toxicity was unsurprising, disruption of a single transporter, CycA, was sufficient to completely overcome the repression of type 3 secretion system activity normally associated with exposure to D-Ser. Despite the fact that this reveals a mechanism by which evolution could drive a pathogen to colonize new niches, interrogation of sequenced E. coli O157:H7 genomes showed a high level of CycA conservation, highlighting a strong selective pressure for functionality. Collectively, these data show that CycA is a critically important conduit for D-Ser uptake that is central to the niche restriction of EHEC.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Roe, Professor Andrew and Connolly, Dr James and O'Boyle, Dr Nicky
Authors: O'Boyle, N., Connolly, J. P.R., Tucker, N. P., and Roe, A. J.
College/School:College of Medical Veterinary and Life Sciences > Institute of Infection Immunity and Inflammation
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:26 August 2020
Copyright Holders:Copyright © 2020 The Authors
First Published:First published in Proceedings of the National Academy of Sciences of the United States of America 117(36):22484-22493
Publisher Policy:Reproduced under a Creative Commons License

University Staff: Request a correction | Enlighten Editors: Update this record

Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
300280The Role of Dietary D-serine in Health and DiseaseAndrew RoeBiotechnology and Biological Sciences Research Council (BBSRC)BB/R006539/1III - Bacteriology