Department of Pediatrics, David Geffen School of Medicine at UCLA, Los Angeles, CA 90073, USA.
Aliment Pharmacol Ther. 2012 Nov;36(10):972-9. doi: 10.1111/apt.12059. Epub 2012 Sep 25.
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.
青霉素类药物抑制细胞壁合成；因此，对于这类抗生素，幽门螺杆菌必须处于分裂状态，才能在根除治疗中发挥作用。确定对不同培养基 pH 值的生长反应可能有助于设计更有效的治疗方案。
确定酸度对细菌生长和氨苄西林杀菌效果的影响。
将幽门螺杆菌在透析室中孵育，悬浮在含有 5 mM 尿素的 1.5L 培养基中，在不同 pH 值下孵育 4、8 或 16 小时，从而模拟未缓冲的胃液。测定基因表达、存活和存活变化。
在 pH 3.0 下，但不在 pH 4.5 或 7.4 下，有~400 个基因的表达减少，包括许多细胞包膜生物合成、细胞分裂和青霉素结合蛋白基因。氨苄西林在 pH 4.5 和 7.4 时具有杀菌作用，但在 pH 3.0 时没有。
氨苄西林在 pH 4.5 和 7.4 时具有杀菌作用，但在 pH 3.0 时没有，这是由于细胞包膜和分裂基因的表达减少，在 pH 3.0 时细胞分裂丧失。因此，在 pH 3.0 下，即胃表面的可能 pH 值下，细菌不分裂，并用氨苄西林治疗时仍能存活。一种更有效的胃酸分泌抑制剂，能将胃 pH 值维持在接近中性 24 小时/天，应能提高阿莫西林的疗效，改善三联疗法，甚至可能允许基于阿莫西林的双联疗法来根除幽门螺杆菌。
