Colloidal bismuth subcitrate (De-Nol) inhibits degradation of gastric mucus by Campylobacter pylori protease

Abstract

There is increased awareness that infection with Campylobacter pylori could be a major factor in the pathogenesis of gastric disease. Here, we present evidence that the extracellular protease elaborated by this bacteria, which causes degradation of gastric mucus, is inhibited by an antiulcer agent, colloidal bismuth subcitrate (CBS; De-Nol). The study was conducted with C. pylori cultured from antral mucosal biopsy specimens of patients undergoing gastroscopy. The grown colonies of bacteria were washed with saline, filtered through sterilization filter, dialyzed, and lyophilized. The powder was used as the enzyme source for proteolytic activity assay employing pig gastric mucus as substrate. Optimum enzymatic activity was obtained at 37 degrees C and at pH 7.0. The apparent Km of C. pylori protease with gastric mucus was 0.71 g/L. Analyses of the degradation products indicated that the protease caused extensive proteolysis of mucus glycoprotein polymer. Introduction of CBS to the incubation mixtures led to a reduction of the rate of mucus degradation. The rate of proteolysis inhibition was proportional to CBS concentration up to 1 X 10(-1) g/L, at which point a 37% reduction in mucus proteolysis was obtained. The Km value for proteolytic degradation of mucus by C. pylori protease in the presence of CBS was 1.25 g/L. The results suggest that CBS is capable of counter-acting the proteolysis of the protective gastric mucus layer by C. pylori.