A highly conserved bacterial d-serine uptake system links host metabolism and virulence

Connolly, J. P. R., Gabrielsen, M., Goldstone, R. J., Grinter, R., Wang, D., Cogdell, R. J. , Walker, D. , Smith, D. G. E. and Roe, A. J. (2016) A highly conserved bacterial d-serine uptake system links host metabolism and virulence. PLoS Pathogens, 12(1), e1005359. (doi:10.1371/journal.ppat.1005359) (PMID:26727373) (PMCID:PMC4699771)

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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.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Roe, Professor Andrew and Walker, Professor Daniel and Wang, Mr Dai and Cogdell, Professor Richard and Connolly, Dr James and Grinter, Mr Rhys and Goldstone, Mr Robert and Smith, Professor David and Gabrielsen, Dr Mads
Authors: Connolly, J. P. R., Gabrielsen, M., Goldstone, R. J., Grinter, R., Wang, D., Cogdell, R. J., Walker, D., Smith, D. G. E., 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:PLoS Pathogens
Publisher:Public Library of Science
ISSN:1553-7374
ISSN (Online):1553-7374
Copyright Holders:Copyright © 2016 Connolly et al.
First Published:First published in PLoS Pathogens 12(1):e1005359
Publisher Policy:Reproduced under a Creative Commons License

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
580941MRC Doctoral Training Grant 2011-2015Mary Beth KneafseyMedical Research Council (MRC)MR/J50032X/1VICE PRINCIPAL RESEARCH & ENTERPRISE