title: A Highly Conserved Bacterial D-Serine Uptake System Links Host Metabolism and Virulence.
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.
authors.affiliation: Institute of Infection, Immunity and Inflammation, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, United Kingdom.
authors.forename: James P R
authors.initials: JP
authors.lastname: Connolly
authors.affiliation: Cancer Research UK Beatson Institute, Glasgow, United Kingdom.
authors.forename: Mads
authors.initials: M
authors.lastname: Gabrielsen
authors.affiliation: School of Life Sciences, Heriot-Watt University, Edinburgh, United Kingdom.
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Goldstone
authors.affiliation: Department of Microbiology, Monash University, Melbourne, Victoria, Australia.
authors.forename: Rhys
authors.initials: R
authors.lastname: Grinter
authors.affiliation: State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, School of Public Health, Xiamen University, Xiamen, Fujian, People's Republic of China.
authors.forename: Dai
authors.initials: D
authors.lastname: Wang
authors.affiliation: Institute of Molecular, Cell and Systems Biology, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, United Kingdom.
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Cogdell
authors.affiliation: Institute of Infection, Immunity and Inflammation, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, United Kingdom.
authors.forename: Daniel
authors.initials: D
authors.lastname: Walker
authors.affiliation: School of Life Sciences, Heriot-Watt University, Edinburgh, United Kingdom.
authors.forename: David G E
authors.initials: DG
authors.lastname: Smith
authors.affiliation: Institute of Infection, Immunity and Inflammation, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, United Kingdom.
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Roe
mesh_terms: D000595:Amino Acid Sequence; D001483:Base Sequence; D002460:Cell Line; D024202:Electrophoretic Mobility Shift Assay; D054324:Enterohemorrhagic Escherichia coli / Q000472:pathogenicity*; D004927:Escherichia coli Infections / Q000378:metabolism / Q000382:microbiology*; D029968:Escherichia coli Proteins / Q000235:genetics / Q000378:metabolism; D015964:Gene Expression Regulation, Bacterial / Q000502:physiology; D054884:Host-Pathogen Interactions / Q000502:physiology*; D006801:Humans; D015151:Immunoblotting; D008856:Microscopy, Fluorescence; D008969:Molecular Sequence Data; D060888:Real-Time Polymerase Chain Reaction; D012694:Serine / Q000378:metabolism*; D000069296:Type III Secretion Systems / Q000378:metabolism*; D014774:Virulence
chemical_list: D029968:Escherichia coli Proteins; D000069296:Type III Secretion Systems; D012694:Serine