title: The complement regulator CD46 is bactericidal to Helicobacter pylori and blocks urease activity.
abstract: OBJECTIVE
  CD46 is a C3b/C4b binding complement regulator and a receptor for several human pathogens. We examined the interaction between CD46 and Helicobacter pylori (a bacterium that colonizes the human gastric mucosa and causes gastritis), peptic ulcers, and cancer.
  
  
  METHODS
  Using gastric epithelial cells, we analyzed a set of H pylori strains and mutants for their ability to interact with CD46 and/or influence CD46 expression. Bacterial interaction with full-length CD46 and small CD46 peptides was evaluated by flow cytometry, fluorescence microscopy, enzyme-linked immunosorbent assay, and bacterial survival analyses.
  
  
  RESULTS
  H pylori infection caused shedding of CD46 into the extracellular environment. A soluble form of CD46 bound to H pylori and inhibited growth, in a dose- and time-dependent manner, by interacting with urease and alkyl hydroperoxide reductase, which are essential bacterial pathogenicity-associated factors. Binding of CD46 or CD46-derived synthetic peptides blocked the urease activity and ability of bacteria to survive in acidic environments. Oral administration of one CD46 peptide eradicated H pylori from infected mice.
  
  
  CONCLUSIONS
  CD46 is an antimicrobial agent that can eradicate H pylori. CD46 peptides might be developed to treat H pylori infection.
authors.affiliation: Department of Genetics, Microbiology and Toxicology, Stockholm University, Stockholm, Sweden.
authors.forename: Rahma
authors.initials: R
authors.lastname: Basmarke-Wehelie
authors.forename: Hong
authors.initials: H
authors.lastname: Sjölinder
authors.forename: Wiktor
authors.initials: W
authors.lastname: Jurkowski
authors.forename: Arne
authors.initials: A
authors.lastname: Elofsson
authors.forename: Anna
authors.initials: A
authors.lastname: Arnqvist
authors.forename: Lars
authors.initials: L
authors.lastname: Engstrand
authors.forename: Matthias
authors.initials: M
authors.lastname: Hagner
authors.forename: Elin
authors.initials: E
authors.lastname: Wallin
authors.forename: Na
authors.initials: N
authors.lastname: Guan
authors.forename: Hasanthi
authors.initials: H
authors.lastname: Kuranasekera
authors.forename: Helena
authors.initials: H
authors.lastname: Aro
authors.forename: Ann-Beth
authors.initials: AB
authors.lastname: Jonsson
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology* / Q000627:therapeutic use; D002460:Cell Line; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004847:Epithelial Cells / Q000166:cytology / Q000378:metabolism / Q000382:microbiology; D005753:Gastric Mucosa / Q000166:cytology / Q000378:metabolism* / Q000382:microbiology; D016481:Helicobacter Infections / Q000188:drug therapy / Q000378:metabolism; D016480:Helicobacter pylori / Q000187:drug effects* / Q000254:growth & development / Q000378:metabolism; D006801:Humans; D051916:Membrane Cofactor Protein / Q000378:metabolism / Q000494:pharmacology* / Q000627:therapeutic use; D051379:Mice; D008817:Mice, Mutant Strains; D054464:Peroxiredoxins / Q000187:drug effects / Q000378:metabolism; D013997:Time Factors; D016896:Treatment Outcome; D014510:Urease / Q000187:drug effects* / Q000378:metabolism*
chemical_list: D000900:Anti-Bacterial Agents; D051916:Membrane Cofactor Protein; D054464:Peroxiredoxins; D014510:Urease