Antimicrobial actions of benzimidazoles against oral streptococci.

OBJECTIVE

Benzimidazoles, such as lansoprazole and omeprazole, are used extensively as proton-pump inhibitors to control stomach acid secretion and also have antimicrobial actions against Helicobacter pylori. Our objective was to determine whether they are potentially useful antimicrobials against oral bacteria.

METHODS

Streptococcus mutans was our main test organism. It was grown in suspension cultures and biofilms. Standard physiologic assays were used to assess inhibitory actions of benzimidazoles.

RESULTS

Benzimidazoles inhibited acid production by S. mutans in suspensions or biofilms. In pH-drop experiments, lansoprazole at a level of only 0.025 mm irreversibly inhibited acid production from glycolysis. Cell uptake of lansoprazole was found to be very pH sensitive and occurred mainly at pH values below about 5, indicating that the protonated form was taken up. Lansoprazole inhibition of glycolysis could be blocked by 2-mercaptoethanol, which suggests that disulfide bonds form between benzimidazoles and protein targets. Identified targets for benzimidazole inhibition included the phosphoenolpyruvate : sugar phosphotransferase system, the glycolytic enzymes aldolase, glyceraldehyde-3-phosphate dehydrogenase, and lactic dehydrogenase, and enzymes such as urease and arginine deiminase. Lansoprazole increased proton permeabilities of S. mutans cells but did not inhibit F-ATPases. Although cells in biofilms were somewhat less sensitive to the agents than those in suspensions, biofilm glycolysis was still markedly inhibited by 0.1 mm lansoprazole. Benzimidazoles are bactericidal, and the oral anaerobes Fusobacterium nucleatum and Prevotella intermedia were more sensitive to killing than was S. mutans.

CONCLUSIONS

Benzimidazoles appear to be useful inhibitors of oral bacteria in acid environments such as progressing caries lesions.