title: The host metabolite D-serine contributes to bacterial niche specificity through gene selection.
abstract: Escherichia coli comprise a diverse array of both commensals and niche-specific pathotypes. The ability to cause disease results from both carriage of specific virulence factors and regulatory control of these via environmental stimuli. Moreover, host metabolites further refine the response of bacteria to their environment and can dramatically affect the outcome of the host-pathogen interaction. Here, we demonstrate that the host metabolite, D-serine, selectively affects gene expression in E. coli O157:H7. Transcriptomic profiling showed exposure to D-serine results in activation of the SOS response and suppresses expression of the Type 3 Secretion System (T3SS) used to attach to host cells. We also show that concurrent carriage of both the D-serine tolerance locus (dsdCXA) and the locus of enterocyte effacement pathogenicity island encoding a T3SS is extremely rare, a genotype that we attribute to an 'evolutionary incompatibility' between the two loci. This study demonstrates the importance of co-operation between both core and pathogenic genetic elements in defining niche specificity.
authors.affiliation: 1] Institute of Infection, Immunity and Inflammation, University of Glasgow, Glasgow, UK [2] School of Life Sciences, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, UK.
authors.forename: James P R
authors.initials: JP
authors.lastname: Connolly
authors.affiliation: 1] Institute of Infection, Immunity and Inflammation, University of Glasgow, Glasgow, UK [2] School of Life Sciences, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, UK.
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Goldstone
authors.affiliation: 1] Institute of Infection, Immunity and Inflammation, University of Glasgow, Glasgow, UK [2] School of Life Sciences, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, UK.
authors.forename: Karl
authors.initials: K
authors.lastname: Burgess
authors.affiliation: Institute of Molecular Cell and Systems Biology, University of Glasgow, Glasgow, UK.
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Cogdell
authors.affiliation: School of Chemistry and Molecular Biosciences and Australian Infectious Diseases Research Centre, University of Queensland, St Lucia, Queensland, Australia.
authors.forename: Scott A
authors.initials: SA
authors.lastname: Beatson
authors.affiliation: Centre for Bacterial Cell Biology, Institute for Cell and Molecular Biosciences, Newcastle University, Newcastle upon Tyne, UK.
authors.forename: Waldemar
authors.initials: W
authors.lastname: Vollmer
authors.affiliation: 1] Institute of Infection, Immunity and Inflammation, University of Glasgow, Glasgow, UK [2] School of Life Sciences, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, UK [3] Moredun Research Institute, Pentlands Science Park, Bush Loan, Edinburgh, Midlothian, UK.
authors.forename: David G E
authors.initials: DG
authors.lastname: Smith
authors.affiliation: 1] Institute of Infection, Immunity and Inflammation, University of Glasgow, Glasgow, UK [2] School of Life Sciences, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, UK.
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Roe
mesh_terms: D019453:Escherichia coli O157 / Q000235:genetics* / Q000378:metabolism / Q000472:pathogenicity; D029968:Escherichia coli Proteins / Q000235:genetics; D015964:Gene Expression Regulation, Bacterial / Q000187:drug effects; D044404:Genomic Islands; D006367:HeLa Cells; D054884:Host-Pathogen Interactions; D006801:Humans; D013014:SOS Response, Genetics; D012694:Serine / Q000494:pharmacology*; D000069296:Type III Secretion Systems / Q000235:genetics; D037521:Virulence Factors / Q000235:genetics
chemical_list: D029968:Escherichia coli Proteins; D000069296:Type III Secretion Systems; D037521:Virulence Factors; D012694:Serine