title: Urea, fluorofamide, and omeprazole treatments alter helicobacter colonization in the mouse gastric mucosa.
abstract: BACKGROUND
  Helicobacter pylori is a causative agent of gastric and duodenal ulcers and gastric cancer. Its urease enzyme allows survival in acid conditions and drives bacterial intracellular metabolism. We aimed to investigate the role of urease in determining the intragastric distribution of Helicobacter species in vivo.
  
  
  METHODS
  The C57BL/6 mouse model of gastritis was used for infection with Helicobacter felis (CS1) or H. pylori (SS1). Urease-modulating compounds urea and/or fluorofamide (urease inhibitor) were administered to mice over 7 days. Concurrent gastric acid inhibition by omeprazole was also examined. Bacterial distribution in the antrum, body, antrum/body, and body/cardia transitional zones was graded "blindly" by histologic evaluation. Bacterial colony counts on corresponding tissue were also conducted.
  
  
  RESULTS
  Urease inhibition by fluorofamide decreased H. pylori survival in most gastric regions (p < .05); however, there were no marked changes to H. felis colonization after this treatment. There was a consistent trend for decreased antral colonization, and an increase in antrum/body transitional zone and body colonization with excess 5% or 6% (w/v) urea treatment. Significant reductions of both Helicobacter species were observed with the co-treatment of urea and fluorofamide (p < .05). Collateral treatment with omeprazole did not alter H. pylori colonization patterns caused by urea/fluorofamide.
  
  
  CONCLUSIONS
  Urease perturbations affect colonization patterns of Helicobacter species. Combined urea and fluorofamide treatment reduced the density of both Helicobacter species in our infection model.
authors.affiliation: School of Biotechnology and Biomolecular Science, University of New South Wales, Sydney, NSW, Australia. laristoteli@Proteome.org.au
authors.forename: Lina Panayiota
authors.initials: LP
authors.lastname: Aristoteli
authors.forename: Jani L
authors.initials: JL
authors.lastname: O'Rourke
authors.forename: Stephen
authors.initials: S
authors.lastname: Danon
authors.forename: Hakan
authors.initials: H
authors.lastname: Larsson
authors.forename: Bjorn
authors.initials: B
authors.lastname: Mellgard
authors.forename: Hazel
authors.initials: H
authors.lastname: Mitchell
authors.forename: Adrian
authors.initials: A
authors.lastname: Lee
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000627:therapeutic use*; D000897:Anti-Ulcer Agents / Q000008:administration & dosage / Q000627:therapeutic use; D001549:Benzamides / Q000008:administration & dosage / Q000627:therapeutic use*; D004791:Enzyme Inhibitors / Q000008:administration & dosage / Q000627:therapeutic use; D005260:Female; D005753:Gastric Mucosa / Q000187:drug effects / Q000382:microbiology*; D016481:Helicobacter Infections / Q000188:drug therapy* / Q000382:microbiology; D044922:Helicobacter felis / Q000187:drug effects / Q000201:enzymology; D016480:Helicobacter pylori / Q000187:drug effects* / Q000201:enzymology; D006863:Hydrogen-Ion Concentration; D051379:Mice; D008807:Mice, Inbred BALB C; D023421:Models, Animal; D009853:Omeprazole / Q000627:therapeutic use*; D014508:Urea / Q000008:administration & dosage / Q000627:therapeutic use*; D014510:Urease / Q000037:antagonists & inhibitors* / Q000378:metabolism
chemical_list: D000900:Anti-Bacterial Agents; D000897:Anti-Ulcer Agents; D001549:Benzamides; D004791:Enzyme Inhibitors; C032764:flurofamide; D014508:Urea; D014510:Urease; D009853:Omeprazole