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

James P. R. Connolly (), Sabrina L. Slater, Nicky O’Boyle, Robert J. Goldstone, Valerie F. Crepin, David Ruano-Gallego, Pawel Herzyk, David G. E. Smith, Gillian R. Douce, Gad Frankel and Andrew J. Roe ()
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James P. R. Connolly: University of Glasgow
Sabrina L. Slater: Imperial College
Nicky O’Boyle: University of Glasgow
Robert J. Goldstone: Heriot-Watt University
Valerie F. Crepin: Imperial College
David Ruano-Gallego: Imperial College
Pawel Herzyk: University of Glasgow, Garscube Estate
David G. E. Smith: Heriot-Watt University
Gillian R. Douce: University of Glasgow
Gad Frankel: Imperial College
Andrew J. Roe: University of Glasgow

Nature Communications, 2018, vol. 9, issue 1, 1-14

Abstract: 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.

Date: 2018
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DOI: 10.1038/s41467-018-06701-4

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