Helicobacter pylori HopH (OipA) and bacterial pathogenicity: genetic and functional genomic analysis of hopH gene polymorphisms

J Infect Dis. 2006 Nov 15;194(10):1346-55. doi: 10.1086/508426. Epub 2006 Oct 10.


Background: Expression of the Helicobacter pylori outer membrane protein HopH is regulated by phase variation within a CT dinucleotide repeat motif of the hopH gene.

Methods: To investigate the importance of HopH for bacterial pathogenicity, we performed a detailed functional genomic and population-based genetic characterization of this contingency locus.

Results: Sequencing of hopH in H. pylori strains from 58 patients revealed that the hopH "on" genotype is linked to bacterial virulence determinants, such as the vacAs1, vacAm1, babA2, and, most strongly, cagA genotypes. hopH mutagenesis resulted in reduced bacterial adherence to gastric epithelia in vitro. Complementation of hopH in trans restored the adherence properties of hopH mutants. Although HopH has been previously linked to proinflammatory epithelial signaling, hopH mutagenesis did not alter epithelial interleukin-8 secretion in vitro. Comparative epithelial gene-expression profiling by cDNA microarrays revealed no significant differences between the wild-type-specific and hopH mutant-specific transcriptomes. By contrast, a large set of genes was differentially regulated in a cag pathogenicity island-dependent manner.

Conclusion: An in-frame hopH gene may be linked to gastroduodenal diseases because of its association with other virulence factors or increased bacterial adherence and colonization. The strong linkage with cagA indicates that HopH may contribute to the fitness of cagA-positive strains in vivo.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adhesins, Bacterial / genetics
  • Amino Acid Sequence
  • Antigens, Bacterial / genetics
  • Antigens, Bacterial / metabolism
  • Bacterial Adhesion / genetics
  • Bacterial Outer Membrane Proteins / chemistry
  • Bacterial Outer Membrane Proteins / genetics*
  • Bacterial Outer Membrane Proteins / physiology*
  • Bacterial Proteins / genetics
  • Bacterial Proteins / metabolism
  • Base Sequence
  • Cell Line, Tumor
  • DNA, Bacterial / chemistry
  • DNA, Bacterial / genetics
  • Gastric Mucosa / metabolism
  • Gastric Mucosa / microbiology
  • Gene Expression Profiling
  • Genetic Complementation Test
  • Helicobacter Infections / microbiology*
  • Helicobacter pylori / genetics*
  • Helicobacter pylori / pathogenicity*
  • Humans
  • Interleukin-8 / biosynthesis
  • Molecular Sequence Data
  • Mutagenesis
  • Oligonucleotide Array Sequence Analysis
  • Polymorphism, Genetic*
  • RNA, Messenger / analysis
  • Sequence Alignment
  • Virulence / genetics


  • Adhesins, Bacterial
  • Antigens, Bacterial
  • BabA protein, Helicobacter pylori
  • Bacterial Outer Membrane Proteins
  • Bacterial Proteins
  • DNA, Bacterial
  • HopH protein, Helicobacter pylori
  • Interleukin-8
  • RNA, Messenger
  • VacA protein, Helicobacter pylori
  • cagA protein, Helicobacter pylori