title: A conserved PapB family member, TosR, regulates expression of the uropathogenic Escherichia coli RTX nonfimbrial adhesin TosA while conserved LuxR family members TosE and TosF suppress motility.
abstract: A heterogeneous subset of extraintestinal pathogenic Escherichia coli (ExPEC) strains, referred to as uropathogenic E. coli (UPEC), causes most uncomplicated urinary tract infections. However, no core set of virulence factors exists among UPEC strains. Instead, the focus of the analysis of urovirulence has shifted to studying broad classes of virulence factors and the interactions between them. For example, the RTX nonfimbrial adhesin TosA mediates adherence to host cells derived from the upper urinary tract. The associated tos operon is well expressed in vivo but poorly expressed in vitro and encodes TosCBD, a predicted type 1 secretion system. TosR and TosEF are PapB and LuxR family transcription factors, respectively; however, no role has been assigned to these potential regulators. Thus, the focus of this study was to determine how TosR and TosEF regulate tosA and affect the reciprocal expression of adhesins and flagella. Among a collection of sequenced UPEC strains, 32% (101/317) were found to encode TosA, and nearly all strains (91% [92/101]) simultaneously carried the putative regulatory genes. Deletion of tosR alleviates tosA repression. The tos promoter was localized upstream of tosR using transcriptional fusions of putative promoter regions with lacZ. TosR binds to this region, affecting a gel shift. A 100-bp fragment 220 to 319 bp upstream of tosR inhibits binding, suggesting localization of the TosR binding site. TosEF, on the other hand, downmodulate motility when overexpressed by preventing the expression of fliC, encoding flagellin. Deletion of tosEF increased motility. Thus, we present an additional example of the reciprocal control of adherence and motility.
authors.affiliation: Department of Microbiology and Immunology, University of Michigan Medical School, 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, Ann Arbor, Michigan, USA.
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Alteri
authors.affiliation: Department of Microbiology and Immunology, University of Michigan Medical School, Ann Arbor, Michigan, USA hmobley@umich.edu.
authors.forename: Harry L T
authors.initials: HL
authors.lastname: Mobley
mesh_terms: D018829:Adhesins, Bacterial / Q000235:genetics; D018830:Adhesins, Escherichia coli / Q000235:genetics; D000595:Amino Acid Sequence; D001427:Bacterial Toxins / Q000235:genetics*; D001665:Binding Sites / Q000235:genetics; D004927:Escherichia coli Infections / Q000235:genetics / Q000382:microbiology; D029968:Escherichia coli Proteins / Q000235:genetics*; D005407:Flagella / Q000235:genetics / Q000382:microbiology; D005408:Flagellin / Q000235:genetics; D015964:Gene Expression Regulation, Bacterial / Q000235:genetics*; D008565:Membrane Proteins / Q000235:genetics*; D008969:Molecular Sequence Data; D009876:Operon / Q000235:genetics; D011401:Promoter Regions, Genetic / Q000235:genetics; D012097:Repressor Proteins / Q000235:genetics*; D016415:Sequence Alignment; D015534:Trans-Activators / Q000235:genetics*; D014157:Transcription Factors / Q000235:genetics*; D014552:Urinary Tract Infections / Q000235:genetics / Q000382:microbiology; D056689:Uropathogenic Escherichia coli / Q000235:genetics*; D037521:Virulence Factors / Q000235:genetics
chemical_list: D018829:Adhesins, Bacterial; D018830:Adhesins, Escherichia coli; D001427:Bacterial Toxins; D029968:Escherichia coli Proteins; D008565:Membrane Proteins; D012097:Repressor Proteins; C000610119:TosR protein, E coli; D015534:Trans-Activators; D014157:Transcription Factors; D037521:Virulence Factors; C116245:atpD protein, E coli; C561978:tosA protein, E coli; C064778:LuxR autoinducer binding proteins; D005408:Flagellin