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Partial characterization and effect of omeprazole on ATPase activity in Helicobacter pylori by using permeabilized
1Department of Cell Biology, Preclinical Research and Development, Astra Hässle AB, Mölndal, Sweden.
Abstract:
ATPase activity in permeabilized cells of Helicobacter pylori as well as those of Helicobacter felis and Campylobacter jejuni was analyzed. The ATPase activities in these cells were most susceptible to sodium azide, fluoroaluminate, and dicyclohexylcarbodiimide, which are typical inhibitors of F ATPases. Optimal values for maximal activity were found to be at approximately pH 6.4, 6.0, and 6.0 for C. jejuni, H. pylori, and H. felis, respectively. The substituted benzimidazole compounds omeprazole, lansoprazole, and Eisai 3810 were found to have no effect on the F ATPase activity of H. pylori at concentrations which are inhibitory for cell growth (MICs). In addition, an extracellular, vanadate-susceptible ATPase activity was detected in H. pylori, which was also relatively insusceptible to the benzimidazole compounds. Thus, the mechanism of killing mediated by omeprazole and related compounds in Helicobacter pylori does not appear to be due to diminished ATPase activity.
Insights
Omeprazole and related drugs do not inhibit Helicobacter pylori ATPase activity. This suggests their mechanism of action against these bacteria does not involve disrupting cellular energy production via ATPase inhibition.
Area of Science:
- Microbiology
- Biochemistry
Background:
- Helicobacter pylori, Helicobacter felis, and Campylobacter jejuni are related bacteria.
- ATPase activity is crucial for cellular energy production.
Purpose of the Study:
- To investigate the effect of omeprazole and related benzimidazole compounds on the ATPase activity of H. pylori, H. felis, and C. jejuni.
- To determine if ATPase inhibition is the mechanism by which these drugs kill Helicobacter pylori.
Main Methods:
- Analyzing ATPase activity in permeabilized bacterial cells.
- Testing the susceptibility of ATPase activity to known inhibitors (sodium azide, fluoroaluminate, dicyclohexylcarbodiimide).
- Evaluating the effect of omeprazole, lansoprazole, and Eisai 3810 on ATPase activity and bacterial growth.
Main Results:
- Bacterial ATPase activity was primarily inhibited by F-ATPase specific inhibitors.
- Optimal pH for maximal ATPase activity varied among the species tested.
- Omeprazole and related compounds did not inhibit F-ATPase activity in H. pylori, even at concentrations that inhibited cell growth.
- An additional, extracellular ATPase activity in H. pylori was also unaffected by these benzimidazole compounds.
Conclusions:
- The mechanism of action for omeprazole and similar drugs against Helicobacter pylori does not appear to be related to the inhibition of ATPase activity.
- Bacterial energy metabolism, specifically F-ATPase, is susceptible to known inhibitors but not to the tested benzimidazole compounds.