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 George Emslie Smith; Gillian R. Douce; Gad Frankel; Andrew J. Roe

doi:10.1038/s41467-018-06701-4

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 George Emslie Smith, Gillian R. Douce, Gad Frankel, Andrew J. Roe

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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.

Original language	English
Article number	4187
Journal	Nature Communications
Volume	9
DOIs	https://doi.org/10.1038/s41467-018-06701-4
Publication status	Published - 10 Oct 2018

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David George Emslie Smith
- David.Smithhw.acuk
- School of Engineering & Physical Sciences - Professor
- School of Engineering & Physical Sciences, Institute of Biological Chemistry, Biophysics and Bioengineering - Professor
Person: Academic (Research & Teaching)

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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., & Roe, A. J. (2018). Host-associated niche metabolism controls enteric infection through fine-tuning the regulation of type 3 secretion. Nature Communications, 9, Article 4187. https://doi.org/10.1038/s41467-018-06701-4

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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.",

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AB - 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.

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

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