title: Expression of the Helicobacter pylori adhesin SabA is controlled via phase variation and the ArsRS signal transduction system.
abstract: Adaptation to the acidic microenvironment, and adherence to mucosal epithelium, are essential for persistent colonization of the human stomach by Helicobacter pylori. The expression of SabA, an adhesin implicated in the ability of H. pylori to adhere to the host gastric epithelium, can be modulated by phase variation via slipped-strand mispairing in repetitive nucleotide tracts located in both the promoter region and the coding region. This study demonstrates the occurrence of phase variation at the sabA locus within individual strains of H. pylori, and among multiple isolates from a single patient. In addition, transcription of sabA is repressed by the acid-responsive ArsRS two-component signal transduction system in vitro. Our results demonstrate that isogenic inactivation of the arsS (jhp0151/HP0165) histidine kinase locus results in a 10-fold SabA-dependent increase in adherence to gastric epithelial cells in strain J99 (contains an in-frame sabA allele), but not in strain 26695 (out-of-frame sabA allele). The combination of transcriptional regulation of the sabA locus by the ArsRS two-component signal-transduction system and the generation of subpopulations harbouring alternate sabA alleles by slipped-strand mispairing during chromosomal replication could permit H. pylori to rapidly adapt to varying microenvironments or host immune responses. As a pathogen with a paucity of regulatory proteins, this dual regulation indicates that SabA expression is a tightly regulated process in H. pylori infection.
authors.affiliation: Department of Biology, The College of William and Mary, Williamsburg, VA 23187-8795, USA.
authors.forename: Andrew C
authors.initials: AC
authors.lastname: Goodwin
authors.affiliation: Department of Biology, The College of William and Mary, Williamsburg, VA 23187-8795, USA.
authors.forename: Daniel M
authors.initials: DM
authors.lastname: Weinberger
authors.affiliation: Department of Biology, The College of William and Mary, Williamsburg, VA 23187-8795, USA.
authors.forename: Christopher B
authors.initials: CB
authors.lastname: Ford
authors.affiliation: Department of Biology, The College of William and Mary, Williamsburg, VA 23187-8795, USA.
authors.forename: Jessica C
authors.initials: JC
authors.lastname: Nelson
authors.affiliation: Department of Biology, The College of William and Mary, Williamsburg, VA 23187-8795, USA.
authors.forename: Jonathan D
authors.initials: JD
authors.lastname: Snider
authors.affiliation: Department of Biology, The College of William and Mary, Williamsburg, VA 23187-8795, USA.
authors.forename: Joshua D
authors.initials: JD
authors.lastname: Hall
authors.affiliation: Department of Biology, The College of William and Mary, Williamsburg, VA 23187-8795, USA.
authors.forename: Catharine I
authors.initials: CI
authors.lastname: Paules
authors.affiliation: Department of Veterans Affairs Medical Center, Nashville, TN 37212, USA.|Division of Gastroenterology and Department of Cancer Biology, Vanderbilt University School of Medicine, Nashville, TN 37232-2279, USA.
authors.forename: Richard M
authors.initials: RM
authors.lastname: Peek
authors.affiliation: Department of Biology, The College of William and Mary, Williamsburg, VA 23187-8795, USA.
authors.forename: Mark H
authors.initials: MH
authors.lastname: Forsyth
mesh_terms: D018829:Adhesins, Bacterial / Q000235:genetics / Q000378:metabolism*; D001422:Bacterial Adhesion; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism*; D045744:Cell Line, Tumor; D005753:Gastric Mucosa / Q000382:microbiology; D015964:Gene Expression Regulation, Bacterial; D016481:Helicobacter Infections / Q000382:microbiology*; D016480:Helicobacter pylori / Q000235:genetics / Q000378:metabolism*; D000071677:Histidine Kinase; D006801:Humans; D010641:Phenotype; D011494:Protein Kinases / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction
chemical_list: D018829:Adhesins, Bacterial; D001426:Bacterial Proteins; C500808:SabA protein, Helicobacter pylori; D011494:Protein Kinases; D000071677:Histidine Kinase