title: Evolutionary adaptation of an AraC-like regulatory protein in Citrobacter rodentium and Escherichia species.
abstract: The evolution of pathogenic bacteria is a multifaceted and complex process, which is strongly influenced by the horizontal acquisition of genetic elements and their subsequent expression in their new hosts. A well-studied example is the RegA regulon of the enteric pathogen Citrobacter rodentium. The RegA regulatory protein is a member of the AraC/XylS superfamily, which coordinates the expression of a gene repertoire that is necessary for full pathogenicity of this murine pathogen. Upon stimulation by an exogenous, gut-associated signal, namely, bicarbonate ions, RegA activates the expression of a series of genes, including virulence factors, such as autotransporters, fimbriae, a dispersin-like protein, and the grlRA operon on the locus of enterocyte effacement pathogenicity island. Interestingly, the genes encoding RegA homologues are distributed across the genus Escherichia, encompassing pathogenic and nonpathogenic subtypes. In this study, we carried out a series of bioinformatic, transcriptional, and functional analyses of the RegA regulons of these bacteria. Our results demonstrated that regA has been horizontally transferred to Escherichia spp. and C. rodentium. Comparative studies of two RegA homologues, namely, those from C. rodentium and E. coli SMS-3-5, a multiresistant environmental strain of E. coli, showed that the two regulators acted similarly in vitro but differed in terms of their abilities to activate the virulence of C. rodentium in vivo, which evidently was due to their differential activation of grlRA. Our data indicate that RegA from C. rodentium has strain-specific adaptations that facilitate infection of its murine host. These findings shed new light on the development of virulence by C. rodentium and on the evolution of virulence-regulatory genes of bacterial pathogens in general.
authors.affiliation: Department of Microbiology and Immunology, University of Melbourne, Peter Doherty Institute for Infection and Immunity, Victoria, Australia.
authors.forename: Aimee
authors.initials: A
authors.lastname: Tan
authors.affiliation: ithree Institute, University of Technology, Sydney, NSW, Australia.
authors.forename: Nicola K
authors.initials: NK
authors.lastname: Petty
authors.affiliation: Department of Microbiology and Immunology, University of Melbourne, Peter Doherty Institute for Infection and Immunity, Victoria, Australia.
authors.forename: Dianna
authors.initials: D
authors.lastname: Hocking
authors.affiliation: Department of Microbiology and Immunology, University of Melbourne, Peter Doherty Institute for Infection and Immunity, Victoria, Australia.
authors.forename: Vicki
authors.initials: V
authors.lastname: Bennett-Wood
authors.affiliation: Walter Eliza Hall Institute of Medical Research, Parkville, Victoria, Australia.
authors.forename: Matthew
authors.initials: M
authors.lastname: Wakefield
authors.affiliation: Department of Microbiology and Immunology, University of Melbourne, Peter Doherty Institute for Infection and Immunity, Victoria, Australia.
authors.forename: Judyta
authors.initials: J
authors.lastname: Praszkier
authors.affiliation: Department of Microbiology and Immunology, University of Melbourne, Peter Doherty Institute for Infection and Immunity, Victoria, Australia.
authors.forename: Marija
authors.initials: M
authors.lastname: Tauschek
authors.affiliation: Department of Microbiology and Immunology, University of Melbourne, Peter Doherty Institute for Infection and Immunity, Victoria, Australia.
authors.forename: Ji
authors.initials: J
authors.lastname: Yang
authors.affiliation: Department of Microbiology and Immunology, University of Melbourne, Peter Doherty Institute for Infection and Immunity, Victoria, Australia Murdoch Children's Research Institute, Royal Children's Hospital, Parkville, Victoria, Australia r.browne@unimelb.edu.au.
authors.forename: Roy
authors.initials: R
authors.lastname: Robins-Browne
mesh_terms: D000818:Animals; D051777:AraC Transcription Factor / Q000235:genetics*; D001426:Bacterial Proteins / Q000235:genetics*; D005075:Biological Evolution; D044082:Citrobacter rodentium / Q000235:genetics* / Q000472:pathogenicity*; D004926:Escherichia coli / Q000235:genetics* / Q000472:pathogenicity; D029968:Escherichia coli Proteins / Q000235:genetics*; D015964:Gene Expression Regulation, Bacterial; D022761:Gene Transfer, Horizontal; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D010750:Phosphoproteins / Q000235:genetics; D010802:Phylogeny; D012097:Repressor Proteins / Q000235:genetics; D037521:Virulence Factors / Q000235:genetics
chemical_list: D051777:AraC Transcription Factor; C497371:AraC protein, E coli; D001426:Bacterial Proteins; D029968:Escherichia coli Proteins; C513429:GrlR protein, E coli; C457340:LEE protein, E coli; D010750:Phosphoproteins; C072722:RegA protein, Bacteria; D012097:Repressor Proteins; D037521:Virulence Factors