The effects of varying acidity on Helicobacter pylori growth and the bactericidal efficacy of ampicillin

Abstract

Summary Background Penicillins inhibit cell wall synthesis; therefore, H. 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. Aim To determine the effect of acidity on bacterial growth and the bactericidal efficacy of ampicillin. Methods H. pylori were incubated in dialysis chambers suspended in 1.5L of media at various pHs with 5mM urea, with or without ampicillin, for 4, 8 or 16 hours, 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. Conclusion 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 non-dividing and persist with ampicillin treatment. A more effective inhibitor of acid secretion that maintains gastric pH near neutrality for 24 hours/day should enhance the efficacy of amoxicillin, improving triple therapy and likely even allowing dual amoxicillin based therapy for H. pylori eradication.

Vonoprazan, a Novel Potassium-Competitive Acid Blocker, Should Be Used for the Helicobacter pylori Eradication Therapy as First Choice: A Large Sample Study of Vonoprazan in Real World Compared with Our Randomized Control Trial Using Second-Generation Proton Pump Inhibitors for Helicobacter pylori Eradication Therapy

“…Some reports revealed the efficacy of vonoprazan [19-22]. This drug is considered to be less affected by CYP2C19 polymorphism because it is mainly metabolized by CYP3A4 [23, 24]. Vonoprazan has been demonstrated to be non-inferior and superior to lansoprazole in primary H. pylori eradication with triple therapy in a phase III randomized, double-blind study [25].…”

The first-line regimens of Helicobacter pylori eradication in Korea

“…PPIs have two major roles in the eradication therapy; one is reducing gastric acid secretion, and the other is increasing bioavailability and activities of antibiotics [14]. In addition, gastric acid secretion is not sufficiently inhibited in extensive metabolizers of PPIs.…”

Gastric Acid-Dependent Diseases: A Twentieth-Century Revolution

“…This reflects a likely adaptation to neutral pH. At acidic pH, ArsS is activated with ArsR phosphorylation and this results in upregulation of ureAB mRNA and consequent increase in acid-protective urease activity hence untreatable at intragastric pH \ 3.0 [44] contributing to the [30 % failure of standard triple therapy in acid hypersecretors. Some adverse effects of PPIs include hypocalcaemia in elderly patients undergoing chronic therapy [45].…”

“…As noted above, at pH 3.0 the organism ceases to grow, developing a persistent phenotype. Potent acid suppression, achieving pH [ 5.0, 24 h/ day, abolishes this persistence [44]. Although current PPIs fall short of this goal, the use of a more effective PPIs such Dig Dis Sci (2014) 59:1358-1369 1367 as the prodrug of omeprazole, AGN904, or the aforementioned long-acting K ?…”