Host-associated niche metabolism controls enteric infection through fine-tuning the regulation of type 3 secretion (original) (raw)

Connolly, J. P.R. et al. (2018) Host-associated niche metabolism controls enteric infection through fine-tuning the regulation of type 3 secretion.Nature Communications, 9, 4187. (doi: 10.1038/s41467-018-06701-4) (PMID:30305622) (PMCID:PMC6180029)

Abstract

Niche-adaptation of a bacterial pathogen hinges on the ability to recognize the complexity of signals from the environment and integrate that information with the regulation of genes critical for infection. Here we report the transcriptome of the attaching and effacing pathogen Citrobacter rodentium during infection of its natural murine host. Pathogen gene expression in vivo was heavily biased towards the virulence factor repertoire and was found to be co-ordinated uniquely in response to the host. Concordantly, we identified the host-specific induction of a metabolic pathway that overlapped with the regulation of virulence. The essential type 3 secretion system and an associated suite of distinct effectors were found to be modulated co-ordinately through a unique mechanism involving metabolism of microbiota-derived 1,2-propanediol, which dictated the ability to colonize the host effectively. This study provides novel insights into how host-specific metabolic adaptation acts as a cue to fine-tune virulence.

Item Type: Articles
Additional Information: This work was supported by a Wellcome Trust Investigator award to Gad Frankel (107057/Z/15/Z), Wellcome Trust ISSF grants (105614/Z/14/Z and 204820/Z/16/Z) and BBSRC funding (BB/M029646/1 & BB/R006539/1) awarded to A.J.R.
Status: Published
Refereed: Yes
Glasgow Author(s) Enlighten ID: Connolly, Dr James and Douce, Dr Gillian and Roe, Professor Andrew and Herzyk, Dr Pawel and O'Boyle, Dr Nicky
Authors: Connolly, J. P.R., Slater, S. L., O'Boyle, N., Goldstone, R. J., Crepin, V. F., Ruano-Gallego, D., Herzyk, P., Smith, D. G. E., Douce, G. R., Frankel, G., and Roe, A. J.
College/School: College of Medical Veterinary and Life Sciences > School of Infection & ImmunityCollege of Medical Veterinary and Life Sciences > School of Molecular Biosciences
Journal Name: Nature Communications
Publisher: Nature Research
ISSN: 2041-1723
ISSN (Online): 2041-1723
Published Online: 10 October 2018
Copyright Holders: Copyright © 2018 The Authors
First Published: First published in Nature Communications 9:4187
Publisher Policy: Reproduced under a Creative Commons license

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Funder and Project Information

1

Institutional Strategic Support Fund (2016)

Anna Dominiczak

204820/Z/16/Z

RI CARDIOVASCULAR & MEDICAL SCIENCES

3

Institutional Strategic Support Fund (ISSF)

Anna Dominiczak

105614/Z/14/Z

RI CARDIOVASCULAR & MEDICAL SCIENCES

1

Where and Why: The Influence of Host Metabolism on Bacterial Niche Specificity

Andrew Roe

BB/M029646/1

III - BACTERIOLOGY

0

The Role of Dietary D-serine in Health and Disease

Andrew Roe

BB/R006539/1

III - Bacteriology

Deposit and Record Details

ID Code: 195717
Depositing User: Ms Rachael Briggs
Datestamp: 11 Sep 2019 10:46
Last Modified: 28 May 2020 22:53
Date of acceptance: 14 September 2018
Date of first online publication: 10 October 2018
Date Deposited: 11 September 2019