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

Artikel i vetenskaplig tidskrift
Författare Jiangyun Sheng
Phuong T M Nguyen
Jeremiah D Baldeck
Jan Olsson
Robert E Marquis
Publicerad i Archives of oral biology
Volym 51
Nummer/häfte 11
Sidor 1015-23
ISSN 0003-9969
Publiceringsår 2006
Publicerad vid Institutionen för odontologi
Sidor 1015-23
Språk en
Länkar dx.doi.org/10.1016/j.archoralbio.20...
Ämnesord 2-Pyridinylmethylsulfinylbenzimidazoles, pharmacology, Amino Acids, metabolism, Aminopeptidases, antagonists & inhibitors, Anaerobiosis, physiology, Anti-Infective Agents, pharmacology, Enzyme Inhibitors, pharmacology, Fermentation, Fructose, metabolism, Fusobacterium nucleatum, drug effects, metabolism, Glucose, Glutamic Acid, metabolism, Humans, Hydrogen-Ion Concentration, Lysine, metabolism, Mouth, microbiology, Oxygen, metabolism, Prevotella intermedia, drug effects, metabolism, Serine, metabolism
Ämneskategorier Cariologi, Oral mikrobiologi

Sammanfattning

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 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. 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 benzimidazoles against bacteria involved in gingivitis.

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