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

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

    Research output: Contribution to journalArticle

    28 Citations (Scopus)
    17 Downloads (Pure)

    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
    JournalPLoS Pathogens
    Volume12
    Issue number1
    DOIs
    Publication statusPublished - 4 Jan 2016

    ASJC Scopus subject areas

    • Microbiology
    • Parasitology
    • Virology
    • Immunology
    • Genetics
    • Molecular Biology

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  • Cite this

    Connolly, J. P. R., Gabrielsen, M., Goldstone, R., Grinter, R., Wang, D., Cogdell, R. J., Walker, D., Smith, D., & 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