title: Gastric antimicrobial peptides fail to eradicate Helicobacter pylori infection due to selective induction and resistance.
abstract: BACKGROUND
  Although antimicrobial peptides protect mucus and mucosa from bacteria, Helicobacter pylori is able to colonize the gastric mucus. To clarify in which extend Helicobacter escapes the antimicrobial defense, we systematically assessed susceptibility and expression levels of different antimicrobial host factors in gastric mucosa with and without H. pylori infection.
  
  
  METHODS
  We investigated the expression levels of HBD1 (gene name DEFB1), HBD2 (DEFB4A), HBD3 (DEFB103A), HBD4 (DEFB104A), LL37 (CAMP) and elafin (PI3) by real time PCR in gastric biopsy samples in a total of 20 controls versus 12 patients colonized with H. pylori. Immunostaining was performed for HBD2 and HBD3. We assessed antimicrobial susceptibility by flow cytometry, growth on blood agar, radial diffusion assay and electron microscopy.
  
  
  RESULTS
  H. pylori infection was associated with increased gastric levels of the inducible defensin HBD2 and of the antiprotease elafin, whereas the expression levels of the constitutive defensin HBD1, inducible HBD3 and LL37 remained unchanged. HBD4 was not expressed in significant levels in gastric mucosa. H. pylori strains were resistant to the defensins HBD1 as well as to elafin, and strain specific minimally susceptible to HBD2, whereas HBD3 and LL37 killed all H. pylori strains effectively. We demonstrated the binding of HBD2 and LL37 on the surface of H. pylori cells. Comparing the antibacterial activity of extracts from H. pylori negative and positive biopsies, we found only a minimal killing against H. pylori that was not increased by the induction of HBD2 in H. pylori positive samples.
  
  
  CONCLUSIONS
  These data support the hypothesis that gastric H. pylori evades the host defense shield to allow colonization.
authors.affiliation: Dr. Margarete Fischer-Bosch-Institute of Clinical Pharmacology and University of Tübingen, Stuttgart, Germany.
authors.forename: Sabine
authors.initials: S
authors.lastname: Nuding
authors.forename: Michael
authors.initials: M
authors.lastname: Gersemann
authors.forename: Yoshio
authors.initials: Y
authors.lastname: Hosaka
authors.forename: Sabrina
authors.initials: S
authors.lastname: Konietzny
authors.forename: Christian
authors.initials: C
authors.lastname: Schaefer
authors.forename: Julia
authors.initials: J
authors.lastname: Beisner
authors.forename: Bjoern O
authors.initials: BO
authors.lastname: Schroeder
authors.forename: Maureen J
authors.initials: MJ
authors.lastname: Ostaff
authors.forename: Katunori
authors.initials: K
authors.lastname: Saigenji
authors.forename: German
authors.initials: G
authors.lastname: Ott
authors.forename: Martin
authors.initials: M
authors.lastname: Schaller
authors.forename: Eduard F
authors.initials: EF
authors.lastname: Stange
authors.forename: Jan
authors.initials: J
authors.lastname: Wehkamp
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D023181:Antimicrobial Cationic Peptides / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology; D054804:Cathelicidins / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology; D060467:Disease Resistance; D052978:Disk Diffusion Antimicrobial Tests; D053492:Elafin / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology; D005260:Female; D005753:Gastric Mucosa / Q000378:metabolism* / Q000382:microbiology* / Q000473:pathology; D005756:Gastritis / Q000235:genetics / Q000378:metabolism / Q000382:microbiology / Q000473:pathology; D005786:Gene Expression Regulation; D016481:Helicobacter Infections / Q000235:genetics / Q000378:metabolism* / Q000382:microbiology*; D016480:Helicobacter pylori / Q000187:drug effects; D006801:Humans; D008297:Male; D008875:Middle Aged; D055815:Young Adult; D023083:beta-Defensins / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology
chemical_list: D023181:Antimicrobial Cationic Peptides; D054804:Cathelicidins; D053492:Elafin; D023083:beta-Defensins
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