title: Genome-wide analysis of transcriptional hierarchy and feedback regulation in the flagellar system of Helicobacter pylori.
abstract: The flagellar system of Helicobacter pylori, which comprises more than 40 mostly unclustered genes, is essential for colonization of the human stomach mucosa. In order to elucidate the complex transcriptional circuitry of flagellar biosynthesis in H. pylori and its link to other cell functions, mutants in regulatory genes governing flagellar biosynthesis (rpoN, flgR, flhA, flhF, HP0244) and whole-genome microarray technology were used in this study. The regulon controlled by RpoN, its activator FlgR (FleR) and the cognate histidine kinase HP0244 (FleS) was characterized on a genome-wide scale for the first time. Seven novel genes (HP1076, HP1233, HP1154/1155, HP0366/367, HP0869) were identified as belonging to RpoN-associated flagellar regulons. The hydrogenase accessory gene HP0869 was the only annotated non-flagellar gene in the RpoN regulon. Flagellar basal body components FlhA and FlhF were characterized as functional equivalents to master regulators in H. pylori, as their absence led to a general reduction of transcripts in the RpoN (class 2) and FliA (class 3) regulons, and of 24 genes newly attributed to intermediate regulons, under the control of two or more promoters. FlhA- and FlhF-dependent regulons comprised flagellar and non-flagellar genes. Transcriptome analysis revealed that negative feedback regulation of the FliA regulon was dependent on the antisigma factor FlgM. FlgM was also involved in FlhA- but not FlhF-dependent feedback control of the RpoN regulon. In contrast to other bacteria, chemotaxis and flagellar motor genes were not controlled by FliA or RpoN. A true master regulator of flagellar biosynthesis is absent in H. pylori, consistent with the essential role of flagellar motility and chemotaxis for this organism.
authors.affiliation: Institute of Hygiene and Microbiology, University of Wuerzburg, Josef-Schneider-Strasse 2, D-97080 Wuerzburg, Germany.
authors.forename: Eike
authors.initials: E
authors.lastname: Niehus
authors.forename: Helga
authors.initials: H
authors.lastname: Gressmann
authors.forename: Fang
authors.initials: F
authors.lastname: Ye
authors.forename: Ralph
authors.initials: R
authors.lastname: Schlapbach
authors.forename: Michaela
authors.initials: M
authors.lastname: Dehio
authors.forename: Christoph
authors.initials: C
authors.lastname: Dehio
authors.forename: Allison
authors.initials: A
authors.lastname: Stack
authors.forename: Thomas F
authors.initials: TF
authors.lastname: Meyer
authors.forename: Sebastian
authors.initials: S
authors.lastname: Suerbaum
authors.forename: Christine
authors.initials: C
authors.lastname: Josenhans
mesh_terms: D001426:Bacterial Proteins / Q000235:genetics / Q000502:physiology; D001483:Base Sequence; D002633:Chemotaxis / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics / Q000502:physiology; D012321:DNA-Directed RNA Polymerases / Q000235:genetics / Q000502:physiology; D025461:Feedback, Physiological; D005407:Flagella / Q000235:genetics / Q000502:physiology*; D020869:Gene Expression Profiling; D015964:Gene Expression Regulation, Bacterial; D005798:Genes, Bacterial; D016480:Helicobacter pylori / Q000235:genetics* / Q000502:physiology*; D000071677:Histidine Kinase; D008565:Membrane Proteins / Q000235:genetics / Q000502:physiology; D008969:Molecular Sequence Data; D020559:Monomeric GTP-Binding Proteins / Q000235:genetics / Q000502:physiology; D009154:Mutation; D020411:Oligonucleotide Array Sequence Analysis; D011401:Promoter Regions, Genetic; D011494:Protein Kinases / Q000235:genetics / Q000502:physiology; D051877:RNA Polymerase Sigma 54; D018085:Regulon; D016415:Sequence Alignment; D012808:Sigma Factor / Q000235:genetics / Q000502:physiology; D015398:Signal Transduction; D014158:Transcription, Genetic
chemical_list: D001426:Bacterial Proteins; D004268:DNA-Binding Proteins; C080688:FlhA protein, Bacteria; C064971:FliA protein, Bacteria; D008565:Membrane Proteins; D012808:Sigma Factor; C071266:FlgM protein, Bacteria; C078317:flhF protein, Bacteria; D011494:Protein Kinases; D000071677:Histidine Kinase; D012321:DNA-Directed RNA Polymerases; D051877:RNA Polymerase Sigma 54; D020559:Monomeric GTP-Binding Proteins