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Colloidal bismuth subcitrate impedes proton entry into Helicobacter pylori and increases the efficacy of growth-dependent antibiotics.
- Source :
-
Alimentary pharmacology & therapeutics [Aliment Pharmacol Ther] 2015 Oct; Vol. 42 (7), pp. 922-33. Date of Electronic Publication: 2015 Aug 04. - Publication Year :
- 2015
-
Abstract
- Background: Successful eradication of Helicobacter pylori is becoming more difficult, mainly due to emerging antibiotic resistance. Treatment regimens containing bismuth have increased efficacy, but the mechanism is unknown. Helicobacter pylori is a neutralophile adapted to survive the acidic gastric environment via acid acclimation, but demonstrates more robust growth at neutral pH. Many antibiotics used to treat H. pylori rely on bacterial growth.<br />Aim: To investigate the mechanism of increased efficacy of bismuth-containing H. pylori treatment regimens.<br />Methods: RNAseq and qPCR, urease activity in permeabilised and intact bacteria, internal pH and membrane potential were measured with and without colloidal bismuth subcitrate (CBS). Bacterial survival was assessed with CBS and/or ampicillin.<br />Results: Genes involved with metabolism and growth were upregulated in the presence of CBS at acidic pH. Urease activity of permeabilised H. pylori at pH 7.4 and 4.5 decreased in the presence of CBS, but intact urease activity decreased only at acidic pH. The fall in cytoplasmic pH with external acidification was diminished by CBS. The increase in membrane potential in response to urea addition at acidic medium pH was unaffected by CBS. The impact of CBS and ampicillin on H. pylori survival was greater than either agent alone.<br />Conclusions: Bismuth is not acting directly on urease or the urea channel. Colloidal bismuth subcitrate impedes proton entry into the bacteria, leading to a decrease in the expected fall in cytoplasmic pH. With cytoplasmic pH remaining within range for increased metabolic activity of a neutralophile, the efficacy of growth-dependent antibiotics is augmented.<br /> (© 2015 John Wiley & Sons Ltd.)
- Subjects :
- Antacids administration & dosage
Antacids pharmacology
Anti-Bacterial Agents administration & dosage
Colloids
Gene Expression Regulation, Bacterial drug effects
Helicobacter Infections metabolism
Helicobacter Infections microbiology
Helicobacter pylori drug effects
Helicobacter pylori genetics
Humans
Hydrogen-Ion Concentration
Ion Transport genetics
Microbial Sensitivity Tests
Microbial Viability drug effects
Organometallic Compounds administration & dosage
Protons
Anti-Bacterial Agents therapeutic use
Helicobacter Infections drug therapy
Helicobacter pylori growth & development
Ion Transport drug effects
Organometallic Compounds pharmacology
Subjects
Details
- Language :
- English
- ISSN :
- 1365-2036
- Volume :
- 42
- Issue :
- 7
- Database :
- MEDLINE
- Journal :
- Alimentary pharmacology & therapeutics
- Publication Type :
- Academic Journal
- Accession number :
- 26238858
- Full Text :
- https://doi.org/10.1111/apt.13346