title: Characterization of virulence factors of mouse-adapted Helicobacter pylori strain SS1 and effects on gastric hydrophobicity.
abstract: Gastric infection with Helicobacter pylori results in chronic active gastritis and in some individuals is associated with complications such as peptic ulceration and gastric cancers. A balance between bacterial factors and host responses may determine disease outcome. The mouse-adapted H. pylori strain SS1 has been utilized as a model to study disease pathogenesis. Although chronic gastritis is observed in this murine model of H. pylori infection, other complications of disease seen in the human host (such as peptic ulceration) are not identified. The objectives of this study were to characterize virulence factors of the mouse-adapted H. pylori strain SS1 and determine host responses to infection. Vacuolating cytotoxin activity of H. pylori strain SS1 was determined after incubation of HEp-2 cells with culture supernatant for 24 hr. Polymerase chain reaction was performed to detect the presence of the cagA and cagE genes. Chemokine responses from human gastric epithelial cells infected with H. pylori SS1 were assessed by measurement of the concentration of interleukin-8 in cell-free supernatants. C57BL/6 and gld mice were infected with strain SS1 or sham-infected. Eight weeks following infection, gastric tissues were obtained for histological analysis and surface hydrophobicity was measured by axisymmetric drop-shape analysis. H. pylori strain SS1 was cytotoxin negative, cagA positive, and cagE positive, but induced only a modest interleukin-8 response (684 +/- 140 pg/ml) from AGS gastric epithelial cells in comparison to a clinical isolate (4170 +/- 410 pg/ml, P < 0.0005). Increased inflammation was observed in the stomachs of H. pylori strain SS1-infected animals compared to uninfected controls. Gastritis was not associated with any disease complications. Despite mucosal inflammation, infected mice did not demonstrate alterations in gastric surface hydrophobicity (42.2 degrees +/- 2.2 degrees and 41.4 degrees +/- 3.2 degrees for C57BL/6 and gld, respectively) compared to uninfected mice (43.2 degrees +/- 2.3 degrees and 39.5 degrees +/- 1.6 degrees, respectively). In conclusion, murine infection with H. pylori SS1, which contains putative bacterial virulence factors, results in gastric inflammation. However, the mucosal changes are not associated with alterations in surface hydrophobicity. Therefore, the mouse model of infection with H. pylori, strain SS1 may not serve as an entirely appropriate model to study host factors associated with disease complications.
authors.affiliation: Division of Gastroenterology and Nutrition, Research Institute, The Hospital for Sick Children, Toronto, Ontario, Canada.
authors.forename: A S
authors.initials: AS
authors.lastname: Day
authors.forename: N L
authors.initials: NL
authors.lastname: Jones
authors.forename: Z
authors.initials: Z
authors.lastname: Policova
authors.forename: H A
authors.initials: HA
authors.lastname: Jennings
authors.forename: E K
authors.initials: EK
authors.lastname: Yau
authors.forename: P
authors.initials: P
authors.lastname: Shannon
authors.forename: A W
authors.initials: AW
authors.lastname: Neumann
authors.forename: P M
authors.initials: PM
authors.lastname: Sherman
mesh_terms: D000818:Animals; D000942:Antigens, Bacterial; D001426:Bacterial Proteins / Q000276:immunology; D001427:Bacterial Toxins / Q000276:immunology; D003602:Cytotoxicity, Immunologic; D004195:Disease Models, Animal; D005260:Female; D005753:Gastric Mucosa / Q000276:immunology; D005756:Gastritis / Q000276:immunology / Q000382:microbiology*; D016481:Helicobacter Infections / Q000276:immunology*; D016480:Helicobacter pylori / Q000145:classification / Q000235:genetics / Q000276:immunology / Q000472:pathogenicity; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D013045:Species Specificity; D014774:Virulence
chemical_list: D000942:Antigens, Bacterial; D001426:Bacterial Proteins; D001427:Bacterial Toxins; C074689:VacA protein, Helicobacter pylori; C080866:cagA protein, Helicobacter pylori