title: The UbiI (VisC) Aerobic Ubiquinone Synthase Is Required for Expression of Type 1 Pili, Biofilm Formation, and Pathogenesis in Uropathogenic Escherichia coli.
abstract: Uropathogenic Escherichia coli (UPEC), which causes the majority of urinary tract infections (UTI), uses pilus-mediated adherence to initiate biofilm formation in the urinary tract. Oxygen gradients within E. coli biofilms regulate expression and localization of adhesive type 1 pili. A transposon mutant screen for strains defective in biofilm formation identified the ubiI (formerly visC) aerobic ubiquinone synthase gene as critical for UPEC biofilm formation. In this study, we characterized a nonpolar ubiI deletion mutant and compared its behavior to that of wild-type bacteria grown under aerobic and anoxic conditions. Consistent with its function as an aerobic ubiquinone-8 synthase, deletion of ubiI in UPEC resulted in reduced membrane potential, diminished motility, and reduced expression of chaperone-usher pathway pili. Loss of aerobic respiration was previously shown to negatively impact expression of type 1 pili. To determine whether this reduction in type 1 pili was due to an energy deficit, wild-type UPEC and the ubiI mutant were compared for energy-dependent phenotypes under anoxic conditions, in which quinone synthesis is undertaken by anaerobic quinone synthases. Under anoxic conditions, the two strains exhibited wild-type levels of motility but produced diminished numbers of type 1 pili, suggesting that the reduction of type 1 pilus expression in the absence of oxygen is not due to a cellular energy deficit. Acute- and chronic-infection studies in a mouse model of UTI revealed a significant virulence deficit in the ubiI mutant, indicating that UPEC encounters enough oxygen in the bladder to induce aerobic ubiquinone synthesis during infection.
  
  
  
  The majority of urinary tract infections are caused by uropathogenic E. coli, a bacterium that can respire in the presence and absence of oxygen. The bladder environment is hypoxic, with oxygen concentrations ranging from 4% to 7%, compared to 21% atmospheric oxygen. This work provides evidence that aerobic ubiquinone synthesis must be engaged during bladder infection, indicating that UPEC bacteria sense and use oxygen as a terminal electron acceptor in the bladder and that this ability drives infection potential despite the fact that UPEC is a facultative anaerobe.
authors.affiliation: Department of Pathology, Microbiology & Immunology, Vanderbilt University School of Medicine, Nashville, Tennessee, USA.
authors.forename: Kyle A
authors.initials: KA
authors.lastname: Floyd
authors.affiliation: Department of Chemical and Biomolecular Engineering, Vanderbilt University, Tennessee, USA.
authors.forename: Courtney A
authors.initials: CA
authors.lastname: Mitchell
authors.affiliation: Department of Pathology, Microbiology & Immunology, Vanderbilt University School of Medicine, Nashville, Tennessee, USA.
authors.forename: Allison R
authors.initials: AR
authors.lastname: Eberly
authors.affiliation: Department of Pathology, Microbiology & Immunology, Vanderbilt University School of Medicine, Nashville, Tennessee, USA.
authors.forename: Spencer J
authors.initials: SJ
authors.lastname: Colling
authors.affiliation: Department of Pathology, Microbiology & Immunology, Vanderbilt University School of Medicine, Nashville, Tennessee, USA.
authors.forename: Ellisa W
authors.initials: EW
authors.lastname: Zhang
authors.affiliation: Department of Molecular, Cellular & Developmental Biology, University of Michigan-Ann Arbor, Ann Arbor, Michigan, USA.
authors.forename: William
authors.initials: W
authors.lastname: DePas
authors.affiliation: Department of Molecular, Cellular & Developmental Biology, University of Michigan-Ann Arbor, Ann Arbor, Michigan, USA.
authors.forename: Matthew R
authors.initials: MR
authors.lastname: Chapman
authors.affiliation: Department of Molecular Microbiology & Microbial Pathogenesis, Washington University School of Medicine in Saint Louis, St. Louis, Missouri, USA.
authors.forename: Matthew
authors.initials: M
authors.lastname: Conover
authors.affiliation: Department of Chemical and Biomolecular Engineering, Vanderbilt University, Tennessee, USA.
authors.forename: Bridget R
authors.initials: BR
authors.lastname: Rogers
authors.affiliation: Department of Molecular Microbiology & Microbial Pathogenesis, Washington University School of Medicine in Saint Louis, St. Louis, Missouri, USA.
authors.forename: Scott J
authors.initials: SJ
authors.lastname: Hultgren
authors.affiliation: Department of Pathology, Microbiology & Immunology, Vanderbilt University School of Medicine, Nashville, Tennessee, USA maria.hadjifrangiskou@vanderbilt.edu.
authors.forename: Maria
authors.initials: M
authors.lastname: Hadjifrangiskou
mesh_terms: D000818:Animals; D018441:Biofilms / Q000254:growth & development*; D029968:Escherichia coli Proteins / Q000235:genetics / Q000378:metabolism*; D005260:Female; D010861:Fimbriae, Bacterial / Q000378:metabolism*; D017353:Gene Deletion; D015964:Gene Expression Regulation, Bacterial / Q000502:physiology; D015971:Gene Expression Regulation, Enzymologic / Q000502:physiology; D008564:Membrane Potentials; D051379:Mice; D008809:Mice, Inbred C3H; D006899:Mixed Function Oxygenases / Q000235:genetics / Q000378:metabolism*; D009154:Mutation; D014552:Urinary Tract Infections / Q000382:microbiology*; D056689:Uropathogenic Escherichia coli / Q000235:genetics / Q000378:metabolism* / Q000472:pathogenicity; D014774:Virulence
chemical_list: D029968:Escherichia coli Proteins; C000619498:UbiI protein, E coli; D006899:Mixed Function Oxygenases