title: Regulation of Expression of Uropathogenic Escherichia coli Nonfimbrial Adhesin TosA by PapB Homolog TosR in Conjunction with H-NS and Lrp.
abstract: Urinary tract infections (UTIs) are a major burden to human health. The overwhelming majority of UTIs are caused by uropathogenic Escherichia coli (UPEC) strains. Unlike some pathogens, UPEC strains do not have a fixed core set of virulence and fitness factors but do have a variety of adhesins and regulatory pathways. One such UPEC adhesin is the nonfimbrial adhesin TosA, which mediates adherence to the epithelium of the upper urinary tract. The tos operon is AT rich, resides on pathogenicity island aspV, and is not expressed under laboratory conditions. Because of this, we hypothesized that tosA expression is silenced by H-NS. Lrp, based on its prominent function in the regulation of other adhesins, is also hypothesized to contribute to tos operon regulation. Using a variety of in vitro techniques, we mapped both the tos operon promoter and TosR binding sites. We have now identified TosR as a dual regulator of the tos operon, which could control the tos operon in association with H-NS and Lrp. H-NS is a negative regulator of the tos operon, and Lrp positively regulates the tos operon. Exogenous leucine also inhibits Lrp-mediated tos operon positive regulation. In addition, TosR binds to the pap operon, which encodes another important UPEC adhesin, P fimbria. Induction of TosR synthesis reduces production of P fimbria. These studies advance our knowledge of regulation of adhesin expression associated with uropathogen colonization of a host.
authors.affiliation: Department of Microbiology and Immunology, University of Michigan Medical School, University of Michigan, Ann Arbor, Michigan, USA.
authors.forename: Michael D
authors.initials: MD
authors.lastname: Engstrom
authors.affiliation: Department of Microbiology and Immunology, University of Michigan Medical School, University of Michigan, Ann Arbor, Michigan, USA hmobley@umich.edu.
authors.forename: Harry L T
authors.initials: HL
authors.lastname: Mobley
mesh_terms: D018830:Adhesins, Escherichia coli / Q000235:genetics / Q000378:metabolism; D001427:Bacterial Toxins / Q000235:genetics / Q000378:metabolism*; D004927:Escherichia coli Infections / Q000382:microbiology*; D029968:Escherichia coli Proteins / Q000235:genetics / Q000378:metabolism*; D036781:Fimbriae Proteins / Q000235:genetics / Q000378:metabolism*; D015964:Gene Expression Regulation, Bacterial; D006801:Humans; D051756:Leucine-Responsive Regulatory Protein / Q000235:genetics / Q000378:metabolism*; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D009876:Operon; D011401:Promoter Regions, Genetic; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D056689:Uropathogenic Escherichia coli / Q000235:genetics / Q000378:metabolism*
chemical_list: D018830:Adhesins, Escherichia coli; D001427:Bacterial Toxins; D029968:Escherichia coli Proteins; C529458:FimG protein, E coli; C497278:Lrp protein, E coli; D008565:Membrane Proteins; D012097:Repressor Proteins; C000610119:TosR protein, E coli; D014157:Transcription Factors; C116245:atpD protein, E coli; C561978:tosA protein, E coli; D051756:Leucine-Responsive Regulatory Protein; D036781:Fimbriae Proteins