title: The Helicobacter pylori flbA flagellar biosynthesis and regulatory gene is required for motility and virulence and modulates urease of H. pylori and Proteus mirabilis.
abstract: Helicobacter pylori and Proteus mirabilis ureases are nickel-requiring metallo-enzymes that hydrolyse urea to NH3 and CO2. In both H. pylori and in an Escherichia coli model of H. pylori urease activity, a high affinity nickel transporter, NixA, is required for optimal urease activity, whereas the urea-dependent UreR positive transcriptional activator governs optimal urease expression in P. mirabilis. The H. pylori flbA gene is a flagellar biosynthesis and regulatory gene that modulates urease activity in the E. coli model of H. pylori urease activity. All flbA mutants of eight strains of H. pylori were non-motile and five had a strain-dependent alteration in urease activity. The flbA gene decreased urease activity 15-fold when expressed in E. coli containing the H. pylori urease locus and the nixA gene; this was reversed by disruption of flbA. The flbA gene decreased nixA transcription. flbA also decreased urease activity three-fold in E. coli containing the P. mirabilis urease locus in a urea- and UreR-dependent fashion. Here the flbA gene repressed the P. mirabilis urease promoter. Thus, FlbA decreased urease activity of both H. pylori and P. mirabilis, but through distinct mechanisms. H. pylori wild-type strain SS1 colonised gerbils at a mean of 5.4 x 10(6) cfu/g of antrum and caused chronic gastritis and lesions in the antrum. In contrast, the flbA mutant did not colonise five of six gerbils and caused no lesions, indicating that motility mediated by flbA was required for colonisation. Because FlbA regulates flagellar biosynthesis and secretion, as well as forming a structural component of the flagellar secretion apparatus, two seemingly unrelated virulence attributes, motility and urease, may be coupled in H. pylori and P. mirabilis and possibly also in other motile, ureolytic bacteria.
authors.forename: David J
authors.initials: DJ
authors.lastname: McGEE
authors.affiliation: Departments of Microbiology & Immunology and †Comparative Medicine, University of South Alabama College of Medicine, Mobile, AL 36688 and *Department of Microbiology & Immunology, University of Maryland School of Medicine, Baltimore, MD 21201, USA.
authors.forename: Christopher
authors.initials: C
authors.lastname: Coker
authors.forename: Traci L
authors.initials: TL
authors.lastname: Testerman
authors.affiliation: Departments of Microbiology & Immunology and †Comparative Medicine, University of South Alabama College of Medicine, Mobile, AL 36688 and *Department of Microbiology & Immunology, University of Maryland School of Medicine, Baltimore, MD 21201, USA.
authors.forename: Janette M
authors.initials: JM
authors.lastname: Harro
authors.affiliation: Departments of Microbiology & Immunology and †Comparative Medicine, University of South Alabama College of Medicine, Mobile, AL 36688 and *Department of Microbiology & Immunology, University of Maryland School of Medicine, Baltimore, MD 21201, USA.
authors.forename: Susan V
authors.initials: SV
authors.lastname: Gibson
authors.affiliation: Departments of Microbiology & Immunology and †Comparative Medicine, University of South Alabama College of Medicine, Mobile, AL 36688 and *Department of Microbiology & Immunology, University of Maryland School of Medicine, Baltimore, MD 21201, USA.
authors.forename: Harry L T
authors.initials: HLT
authors.lastname: Mobley
mesh_terms: D000818:Animals; D001426:Bacterial Proteins / Q000096:biosynthesis* / Q000235:genetics*; D027682:Cation Transport Proteins / Q000235:genetics; D002908:Chronic Disease; D004195:Disease Models, Animal; D004926:Escherichia coli / Q000235:genetics; D005407:Flagella / Q000235:genetics / Q000378:metabolism*; D005753:Gastric Mucosa / Q000473:pathology; D005756:Gastritis / Q000382:microbiology; D017353:Gene Deletion; D015964:Gene Expression Regulation, Bacterial; D005822:Genetic Vectors; D005849:Gerbillinae; D016481:Helicobacter Infections / Q000382:microbiology* / Q000473:pathology; D016480:Helicobacter pylori / Q000235:genetics / Q000378:metabolism / Q000472:pathogenicity* / Q000502:physiology*; D008297:Male; D009068:Movement; D011513:Proteus mirabilis / Q000378:metabolism*; D015534:Trans-Activators / Q000494:pharmacology; D014158:Transcription, Genetic; D014456:Ulcer / Q000473:pathology; D014508:Urea / Q000494:pharmacology; D014510:Urease / Q000378:metabolism*; D014774:Virulence
chemical_list: D001426:Bacterial Proteins; D027682:Cation Transport Proteins; C095257:NixA protein, Helicobacter pylori; D015534:Trans-Activators; C119767:UreR protein, bacteria; C489915:flbA protein, Helicobacter pylori; D014508:Urea; D014510:Urease