The effects of varying acidity on Helicobacter pylori growth and the bactericidal efficacy of ampicillin
Article first published online: 25 SEP 2012
© 2012 Blackwell Publishing Ltd
Alimentary Pharmacology & Therapeutics
Volume 36, Issue 10, pages 972–979, November 2012
How to Cite
Marcus, E. A., Inatomi, N., Nagami, G. T., Sachs, G. and Scott, D. R. (2012), The effects of varying acidity on Helicobacter pylori growth and the bactericidal efficacy of ampicillin. Alimentary Pharmacology & Therapeutics, 36: 972–979. doi: 10.1111/apt.12059
- Issue published online: 16 OCT 2012
- Article first published online: 25 SEP 2012
- Manuscript Revised: 9 SEP 2012
- Manuscript Accepted: 9 SEP 2012
- Manuscript Revised: 6 SEP 2012
- Manuscript Received: 8 AUG 2012
- USVA. Grant Numbers: P30 DK41301, K12 HD034610, DK053462, 1I01BX001006
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.
To determine the effects of acidity on bacterial growth and the bactericidal efficacy of ampicillin.
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.
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.
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.