title: The effect of the cag pathogenicity island on binding of Helicobacter pylori to gastric epithelial cells and the subsequent induction of apoptosis.
abstract: BACKGROUND
  Helicobacter pylori infection leads to gastritis, peptic ulcer, and gastric cancer, in part due to epithelial damage following bacteria binding to the epithelium. Infection with cag pathogenicity island (PAI) bearing strains of H. pylori is associated with increased gastric inflammation and a higher incidence of gastroduodenal diseases. It is now known that various effector molecules are injected into host epithelial cells via a type IV secretion apparatus, resulting in cytoskeletal changes and chemokine secretion. Whether binding of bacteria and subsequent apoptosis of gastric epithelial cells are altered by cag PAI status was examined in this study.
  
  
  METHODS
  AGS, Kato III, and N87 human gastric epithelial cell lines were incubated with cag PAI-positive or cag PAI-negative strains of H. pylori in the presence or absence of clarithromycin. Binding was evaluated by flow cytometry and scanning electron microscopy. Apoptosis was assessed by detection of DNA degradation and ELISA detection of exposed histone residues.
  
  
  RESULTS
  cag PAI-negative strains bound to gastric epithelial cells to the same extent as cag PAI-positive strains. Both cag PAI-positive and cag PAI-negative strains induced apoptosis. However, cag PAI-positive strains induced higher levels of DNA degradation. Incubation with clarithromycin inactivated H. pylori but did not affect binding. However, pretreatment with clarithromycin decreased infection-induced apoptosis.
  
  
  CONCLUSIONS
  cag PAI status did not affect binding of bacteria to gastric epithelial cells but cag PAI-positive H. pylori induced apoptosis more rapidly than cag PAI-negative mutant strains, suggesting that H. pylori binding and subsequent apoptosis are differentially regulated with regard to bacterial properties.
authors.affiliation: Department of Pediatrics, University of Texas Medical Branch at Galveston, TX, USA.
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Minohara
authors.forename: David K
authors.initials: DK
authors.lastname: Boyd
authors.forename: Hal K
authors.initials: HK
authors.lastname: Hawkins
authors.forename: Peter B
authors.initials: PB
authors.lastname: Ernst
authors.forename: Janak
authors.initials: J
authors.lastname: Patel
authors.forename: Sheila E
authors.initials: SE
authors.lastname: Crowe
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology; D017209:Apoptosis; D001422:Bacterial Adhesion / Q000235:genetics*; D001426:Bacterial Proteins / Q000235:genetics / Q000502:physiology*; D002460:Cell Line; D017291:Clarithromycin / Q000494:pharmacology; D053938:DNA Fragmentation; D005753:Gastric Mucosa / Q000166:cytology / Q000382:microbiology*; D017353:Gene Deletion; D044404:Genomic Islands; D016480:Helicobacter pylori / Q000187:drug effects / Q000235:genetics / Q000472:pathogenicity*; D006801:Humans
chemical_list: D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D017291:Clarithromycin