D-serine induces distinct transcriptomes in diverse Escherichia coli pathotypes

Connolly, J. P.R., Turner, N. C.A., Hallam, J., Rimbi, P. T., Flett, T., McCormack, M. J., Roe, A. J. and O'Boyle, N. (2021) D-serine induces distinct transcriptomes in diverse Escherichia coli pathotypes. Microbiology, 167(10), 001093. (doi: 10.1099/mic.0.001093) (PMID:34623236)

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Appropriate interpretation of environmental signals facilitates niche specificity in pathogenic bacteria. However, the responses of niche-specific pathogens to common host signals are poorly understood. D-serine (D-ser) is a toxic metabolite present in highly variable concentrations at different colonisation sites within the human host that we previously found is capable of inducing changes in gene expression. In this study, we made the striking observation that the global transcriptional response of three Escherichia coli pathotypes - enterohaemorrhagic E. coli (EHEC), uropathogenic E. coli (UPEC) and neonatal meningitis associated E. coli (NMEC) - to D-ser was highly distinct. In fact, we identified no single differentially expressed gene common to all three strains. We observed the induction of ribosome-associated genes in extraintestinal pathogens UPEC and NMEC only, and the induction of purine metabolism genes in gut-restricted EHEC and UPEC indicating distinct transcriptional responses to a common signal. UPEC and NMEC encode dsdCXA – a genetic locus required for the detoxification and hence normal growth in the presence of D-ser. Specific transcriptional responses were induced in strains accumulating D-ser (WT EHEC and UPEC/NMEC mutants lacking the D-ser-responsive transcriptional activator DsdC), corroborating the notion that D-ser is an unfavourable metabolite if not metabolized. Importantly, many of the UPEC-associated transcriptome alterations correlate with published data on the urinary transcriptome, supporting the hypothesis that D-ser sensing forms a key part of urinary niche adaptation in this pathotype. Collectively, our results demonstrate distinct pleiotropic responses to a common metabolite in diverse E. coli pathotypes, with important implications for niche selectivity.

Item Type:Articles
Glasgow Author(s) Enlighten ID:McCormack, Mhairi and Turner, Natasha and Connolly, Dr James and Roe, Professor Andrew and Hallam, Miss Jennifer and O'Boyle, Dr Nicky and Rimbi, Patricia
Authors: Connolly, J. P.R., Turner, N. C.A., Hallam, J., Rimbi, P. T., Flett, T., McCormack, M. J., Roe, A. J., and O'Boyle, N.
College/School:College of Medical Veterinary and Life Sciences > Institute of Infection Immunity and Inflammation
College of Medical Veterinary and Life Sciences > School of Life Sciences
Journal Name:Microbiology
Publisher:Microbiology Society
ISSN (Online):1465-2080
Copyright Holders:Copyright © 2021 The Authors
First Published:First published in Microbiology 167(10):001093
Publisher Policy:Reproduced in accordance with the copyright policy of the publisher
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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
172251Where and Why: The Influence of Host Metabolism on Bacterial Niche SpecificityRichard CogdellBiotechnology and Biological Sciences Research Council (BBSRC)BB/M029646/1Institute of Infection, Immunity & Inflammation
300280The Role of Dietary D-serine in Health and DiseaseAndrew RoeBiotechnology and Biological Sciences Research Council (BBSRC)BB/R006539/1III - Bacteriology