A Highly Conserved Bacterial D-Serine Uptake System Links Host Metabolism and Virulence

James P R Connolly, Mads Gabrielsen, Robert J. Goldstone, Rhys Grinter, Dai-Wei Wang, Richard J. Cogdell, Daniel Walker, David G E Smith, Andrew J. Roe

Research output: Contribution to journalArticleResearchpeer-review

Abstract

The ability of any organism to sense and respond to challenges presented in the environment is critically important for promoting or restricting colonization of specific sites. Recent work has demonstrated that the host metabolite D-serine has the ability to markedly influence the outcome of infection by repressing the type III secretion system of enterohaemorrhagic Escherichia coli (EHEC) in a concentration-dependent manner. However, exactly how EHEC monitors environmental D-serine is not understood. In this work, we have identified two highly conserved members of the E. coli core genome, encoding an inner membrane transporter and a transcriptional regulator, which collectively help to “sense” levels of D-serine by regulating its uptake from the environment and in turn influencing global gene expression. Both proteins are required for full expression of the type III secretion system and diversely regulated prophage-encoded effector proteins demonstrating an important infection-relevant adaptation of the core genome. We propose that this system acts as a key safety net, sampling the environment for this metabolite, thereby promoting colonization of EHEC to favorable sites within the host.

Original languageEnglish
Article numbere1005359
Number of pages29
JournalPLoS Pathogens
Volume12
Issue number1
DOIs
Publication statusPublished - 2016

Cite this

Connolly, J. P. R., Gabrielsen, M., Goldstone, R. J., Grinter, R., Wang, D-W., Cogdell, R. J., ... Roe, A. J. (2016). A Highly Conserved Bacterial D-Serine Uptake System Links Host Metabolism and Virulence. PLoS Pathogens, 12(1), [e1005359]. https://doi.org/10.1371/journal.ppat.1005359
Connolly, James P R ; Gabrielsen, Mads ; Goldstone, Robert J. ; Grinter, Rhys ; Wang, Dai-Wei ; Cogdell, Richard J. ; Walker, Daniel ; Smith, David G E ; Roe, Andrew J. / A Highly Conserved Bacterial D-Serine Uptake System Links Host Metabolism and Virulence. In: PLoS Pathogens. 2016 ; Vol. 12, No. 1.
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Connolly, JPR, Gabrielsen, M, Goldstone, RJ, Grinter, R, Wang, D-W, Cogdell, RJ, Walker, D, Smith, DGE & Roe, AJ 2016, 'A Highly Conserved Bacterial D-Serine Uptake System Links Host Metabolism and Virulence', PLoS Pathogens, vol. 12, no. 1, e1005359. https://doi.org/10.1371/journal.ppat.1005359

A Highly Conserved Bacterial D-Serine Uptake System Links Host Metabolism and Virulence. / Connolly, James P R; Gabrielsen, Mads; Goldstone, Robert J.; Grinter, Rhys; Wang, Dai-Wei; Cogdell, Richard J.; Walker, Daniel; Smith, David G E; Roe, Andrew J.

In: PLoS Pathogens, Vol. 12, No. 1, e1005359, 2016.

Research output: Contribution to journalArticleResearchpeer-review

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