Antimicrobial actions of benzimidazoles against the oral anaerobes Fusobacterium nucleatum and Prevotella intermedia

Background/objective: Benzimidazoles are widely used as proton-pump inhibitors to control. stomach hyperacidity and have been found also to have antimicrobial actions against Helicobacter pylori and oral streptococci. Our primary aim was to determine if they are active also against oral anaerobes associated with gingivitis. Our major focus was on catabolism because it Leads to production of inflammatory metabolites such as butyrate and ammonia. The benzimiclazoles are effective in the protonated form at acid pH values and cause irreversible inhibition of enzymes associated with formation of drug-target disulfide bonds. Methods: Fusobacterium nucleatum ATCC 25586 and Prevotella intermedia ATCC 25611 were grown anaerobically in suspension cultures, harvested, washed and exposed to the benzimiclazole lansoprazole at pH values of 4 or 5 before being washed and used for standard assays to detect inhibition of catabolic functions, uptake of the agent and lethality. Results: Lansoprazote was found to be a bacteriostatic, multi-target antimicrobial against F nucleatum under anaerobic conditions inhibitory for amino acid fermentation and also for giycolysis of glucose or fructose. ID50 values for fermentation of amino acids and dipepticles; by F nucleatum ranged from 0.05 mM for lysine to 0.25 mM for serine. Fructose catabolism was highly sensitive with an ID50 value of 0.03 mM apparently related to high sensitivity of the phosphoenolpyruvate:fructose phosphotransferase system, while the ID50 for glucose catabolism by intact celis was some 0.07 mM. Fermentation of aspartate or aspartylaspartate by P intermedia was found to be tansoprazote-sensitive with ID50 values of about 0.18 and 0.20 mM, respectively. Conclusion: Catabolism of amino acids, dipeptides and sugars by oral anaerobes associated with gingivitis are sensitive to the inhibitory actions of lansoprazole. Thus, catabolic pathways are potential targets for use of benzimidazotes against bacteria involved in gingivitis. (c) 2006 Elsevier Ltd. All rights reserved.