Helicobacter pylori disulphide reductases: role in metronidazole reduction

Disulphide reductases play an important role in maintaining intracellular redox potential. Three disulphide reductase activities were identified in Helicobacter pylori, which used dithiobis-2-nitrobenzoic acid, glutathione or l-cystine and ferredoxin as substrates. The kinetic parameters of these activities were determined and it was demonstrated that the reductase activities were inhibited by the presence of metronidazole. Substrate competition experiments served to show inhibition of metronidazole reduction by dithiobis-2-nitrobenzoic acid, glutathione and ferredoxin in lysates from metronidazole susceptible and resistant matched pairs of strains. The study demonstrated that the activities of three disulphide reductases were modulated by the presence of metronidazole, and that metronidazole reduction was inhibited by the presence of disulphide reductase substrates.