Review article: the control of gastric acid and Helicobacter pylori eradication

• Published in: Alimentary pharmacology & therapeutics Vol. 14; no. 11; pp. 1383 - 1401
• Main Authors: Sachs, G, Shin, J M, Munson, K, Vagin, O, Lambrecht, N, Scott, D R, Weeks, D L, Melchers, K
• Format: Journal Article
• Language: English
• Published: England 01.11.2000
• Subjects: Gastric Acid - metabolism; H(+)-K(+)-Exchanging ATPase - drug effects; H(+)-K(+)-Exchanging ATPase - physiology; Helicobacter Infections - drug therapy; Helicobacter pylori - drug effects; Humans; Hydrogen-Ion Concentration; Peptic Ulcer - drug therapy; Peptic Ulcer - microbiology; Proton Pump Inhibitors; Urease - genetics; Urease - physiology
• ISSN: 0269-2813
• DOI: 10.1046/j.1365-2036.2000.00837.x

This review focuses on the gastric acid pump as a therapeutic target for the control of acid secretion in peptic ulcer and gastro-oesophageal reflux disease. The mechanism of the proton pump inhibitors is discussed as well as their clinical use. The biology of Helicobacter pylori as a gastric denizen is then discussed, with special regard to its mechanisms of acid resistance. Here the properties of the products of the urease gene clusters, ureA, B and ureI, E, F, G and H are explored in order to explain the unique location of this pathogen. The dominant requirement for acid resistance is the presence of a proton gated urea transporter, UreI, which increases access of gastric juice urea to the intrabacterial urease 300-fold. This enables rapid and continuous buffering of the bacterial periplasm to approximately pH 6.0, allowing acid resistance and growth at acidic pH in the presence of 1 mM urea. A hypothesis for the basis of combination therapy for eradication is also presented.