Expression of the Helicobacter pylori adhesin SabA is controlled via phase variation and the ArsRS signal transduction system

Andrew C. Goodwin, Daniel M. Weinberger, Christopher B. Ford, Jessica C. Nelson, Jonathan D. Snider, Joshua D. Hall, Catharine I. Paules, Richard M. Peek, Mark H. Forsyth

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Pages (from-to)2231-2240
Number of pages10
JournalMicrobiology
Volume154
Issue number8
DOIs
StatePublished - Sep 11 2008

ASJC Scopus subject areas

  • Microbiology

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    Goodwin, A. C., Weinberger, D. M., Ford, C. B., Nelson, J. C., Snider, J. D., Hall, J. D., Paules, C. I., Peek, R. M., & Forsyth, M. H. (2008). Expression of the Helicobacter pylori adhesin SabA is controlled via phase variation and the ArsRS signal transduction system. Microbiology, 154(8), 2231-2240. https://doi.org/10.1099/mic.0.2007/016055-0