title: The effects of varying acidity on Helicobacter pylori growth and the bactericidal efficacy of ampicillin.
abstract: BACKGROUND
  Penicillins inhibit cell wall synthesis; therefore, Helicobacter pylori must be dividing for this class of antibiotics to be effective in eradication therapy. Identifying growth responses to varying medium pH may allow design of more effective treatment regimens.
  
  
  OBJECTIVE
  To determine the effects of acidity on bacterial growth and the bactericidal efficacy of ampicillin.
  
  
  METHODS
  H. pylori were incubated in dialysis chambers suspended in 1.5-L of media at various pHs with 5 mM urea, with or without ampicillin, for 4, 8 or 16 h, thus mimicking unbuffered gastric juice. Changes in gene expression, viability and survival were determined.
  
  
  RESULTS
  At pH 3.0, but not at pH 4.5 or 7.4, there was decreased expression of ~400 genes, including many cell envelope biosynthesis, cell division and penicillin-binding protein genes. Ampicillin was bactericidal at pH 4.5 and 7.4, but not at pH 3.0.
  
  
  CONCLUSIONS
  Ampicillin is bactericidal at pH 4.5 and 7.4, but not at pH 3.0, due to decreased expression of cell envelope and division genes with loss of cell division at pH 3.0. Therefore, at pH 3.0, the likely pH at the gastric surface, the bacteria are nondividing and persist with ampicillin treatment. A more effective inhibitor of acid secretion that maintains gastric pH near neutrality for 24 h/day should enhance the efficacy of amoxicillin, improving triple therapy and likely even allowing dual amoxicillin-based therapy for H. pylori eradication.
authors.affiliation: Department of Pediatrics, David Geffen School of Medicine at UCLA, Los Angeles, CA 90073, USA.
authors.forename: E A
authors.initials: EA
authors.lastname: Marcus
authors.forename: N
authors.initials: N
authors.lastname: Inatomi
authors.forename: G T
authors.initials: GT
authors.lastname: Nagami
authors.forename: G
authors.initials: G
authors.lastname: Sachs
authors.forename: D R
authors.initials: DR
authors.lastname: Scott
mesh_terms: D000667:Ampicillin / Q000494:pharmacology*; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D005750:Gastric Juice; D016480:Helicobacter pylori / Q000187:drug effects* / Q000254:growth & development; D006801:Humans; D006863:Hydrogen-Ion Concentration; D016133:Polymerase Chain Reaction; D014508:Urea / Q000494:pharmacology
chemical_list: D000900:Anti-Bacterial Agents; D000667:Ampicillin; D014508:Urea