title: RegR virulence regulon of rabbit-specific enteropathogenic Escherichia coli strain E22.
abstract: AraC-like regulators play a key role in the expression of virulence factors in enteric pathogens, such as enteropathogenic Escherichia coli (EPEC), enterotoxigenic E. coli, enteroaggregative E. coli, and Citrobacter rodentium. Bioinformatic analysis of the genome of rabbit-specific EPEC (REPEC) strain E22 (O103:H2) revealed the presence of a gene encoding an AraC-like regulatory protein, RegR, which shares 71% identity to the global virulence regulator, RegA, of C. rodentium. Microarray analysis demonstrated that RegR exerts 25- to 400-fold activation on transcription of several genes encoding putative virulence-associated factors, including a fimbrial operon (SEF14), a serine protease, and an autotransporter adhesin. These observations were confirmed by proteomic analysis of secreted and heat-extracted surface-associated proteins. The mechanism of RegR-mediated activation was investigated by using its most highly upregulated gene target, sefA. Transcriptional analyses and electrophoretic mobility shift assays showed that RegR activates the expression of sefA by binding to a region upstream of the sefA promoter, thereby relieving gene silencing by the global regulatory protein H-NS. Moreover, RegR was found to contribute significantly to virulence in a rabbit infection experiment. Taken together, our findings indicate that RegR controls the expression of a series of accessory adhesins that significantly enhance the virulence of REPEC strain E22.
authors: Department of Microbiology and Immunology, The University of Melbourne, Victoria, Australia.
authors: Yogitha N
authors: YN
authors: Srikhanta
authors: Dianna M
authors: DM
authors: Hocking
authors: Judyta
authors: J
authors: Praszkier
authors: Matthew J
authors: MJ
authors: Wakefield
authors: Roy M
authors: RM
authors: Robins-Browne
authors: Ji
authors: J
authors: Yang
authors: Marija
authors: M
authors: Tauschek
mesh_terms: D000818:Animals; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism*; D019295:Computational Biology; D004269:DNA, Bacterial / Q000378:metabolism; D004195:Disease Models, Animal; D024202:Electrophoretic Mobility Shift Assay; D054308:Enteropathogenic Escherichia coli / Q000235:genetics* / Q000472:pathogenicity*; D004927:Escherichia coli Infections / Q000382:microbiology / Q000473:pathology; D029968:Escherichia coli Proteins / Q000032:analysis; D036781:Fimbriae Proteins / Q000096:biosynthesis / Q000235:genetics; D020869:Gene Expression Profiling; D015964:Gene Expression Regulation, Bacterial; D046228:Microarray Analysis; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D020543:Proteome / Q000032:analysis; D011817:Rabbits; D018085:Regulon; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic; D037521:Virulence Factors / Q000096:biosynthesis* / Q000235:genetics
chemical_list: D001426:Bacterial Proteins; D004269:DNA, Bacterial; D029968:Escherichia coli Proteins; D020543:Proteome; C113722:RegR protein, bacteria; D014157:Transcription Factors; D037521:Virulence Factors; D036781:Fimbriae Proteins