Antimicrobial actions of benzimidazoles against the oral anaerobes Fusobacterium nucleatum and Prevotella intermedia.
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 benzimidazoles 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 benzimidazole 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
Lansoprazole was found to be a bacteriostatic, multi-target antimicrobial against F. nucleatum under anaerobic conditions inhibitory for amino acid fermentation and also for glycolysis of glucose or fructose. ID(50) values for fermentation of amino acids and dipeptides by F. nucleatum ranged from 0.05 mM for lysine to 0.25 mM for serine. Fructose catabolism was highly sensitive with an ID(50) value of 0.03 mM apparently related to high sensitivity of the phosphoenolpyruvate:fructose phosphotransferase system, while the ID(50) for glucose catabolism by intact cells was some 0.07 mM. Fermentation of aspartate or aspartylaspartate by P. intermedia was found to be lansoprazole-sensitive with ID(50) values of about 0.18 and 0.20 mM, respectively.


CONCLUSIONS
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 benzimidazoles against bacteria involved in gingivitis.
Sheng
Jiangyun
J
Department of Microbiology and Immunology and Center for Oral Biology, The University of Rochester Medical Center, Rochester, NY 14642-8672, USA.
Nguyen
Phuong T M
PT
Baldeck
Jeremiah D
JD
Olsson
Jan
J
Marquis
Robert E
RE
D053799:2-Pyridinylmethylsulfinylbenzimidazoles / Q000494:pharmacology*; D000596:Amino Acids / Q000378:metabolism; D000626:Aminopeptidases / Q000037:antagonists & inhibitors; D000693:Anaerobiosis / Q000502:physiology; D000890:Anti-Infective Agents / Q000494:pharmacology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005285:Fermentation; D005632:Fructose / Q000378:metabolism; D016967:Fusobacterium nucleatum / Q000187:drug effects* / Q000378:metabolism; D005947:Glucose; D018698:Glutamic Acid / Q000378:metabolism; D006801:Humans; D006863:Hydrogen-Ion Concentration; D064747:Lansoprazole; D008239:Lysine / Q000378:metabolism; D009055:Mouth / Q000382:microbiology*; D010100:Oxygen / Q000378:metabolism; D018713:Prevotella intermedia / Q000187:drug effects* / Q000378:metabolism; D012694:Serine / Q000378:metabolism
D053799:2-Pyridinylmethylsulfinylbenzimidazoles; D000596:Amino Acids; D000890:Anti-Infective Agents; D004791:Enzyme Inhibitors; D064747:Lansoprazole; D005632:Fructose; D018698:Glutamic Acid; D012694:Serine; D000626:Aminopeptidases; D005947:Glucose; D008239:Lysine; D010100:Oxygen