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

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)

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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 > Institute of Infection Immunity and Inflammation
College of Medical Veterinary and Life Sciences > Institute of Molecular Cell and Systems Biology
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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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
742591Institutional Strategic Support Fund (2016)Anna DominiczakWellcome Trust (WELLCOTR)204820/Z/16/ZRI CARDIOVASCULAR & MEDICAL SCIENCES
623593Institutional Strategic Support Fund (ISSF)Anna DominiczakWellcome Trust (WELLCOTR)105614/Z/14/ZRI CARDIOVASCULAR & MEDICAL SCIENCES
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