title: Action of agents on glucosyltransferases from Streptococcus mutans in solution and adsorbed to experimental pellicle.
abstract: Glucosyltransferase (Gtf) activity mediates sucrose-dependent adherence of mutans streptococci to the tooth surface, is essential for the cariogenicity of these micro-organisms, and contributes significantly to the exopolysaccharide component of the dental-plaque matrix. Clearly, agents that inhibit Gtfs could have therapeutic benefit. Here the effects of agents that inhibit Gtfs in solution and adsorbed to a surface were explored. Various classes of chemical reagents were tested for their ability to inhibit the enzymes responsible for insoluble-glucan synthesis (GtfB), insoluble/soluble glucan synthesis (GtfC), and soluble-glucan (GtfD) from Streptococcus mutans. Standard inhibition assays were done with Gtf enzyme in solution or with Gtf adsorbed to parotid saliva-coated hydroxylapatite (surface phase). Reagents tested included the metallic cations Li+, Zn2+, Cu2+, Fe2+ and Fe3+; the oxidizing compounds hypochlorite, Rose Bengal, perborate, and sodium-meta-periodate; and a panel of sugars and sugar analogues including sorbitol, xylitol, 1',4',6' trideoxy-trichloro-galactosucrose (TGS), and 1-deoxynojirimycin (dNJ). In solution, Gtf activity was inhibited significantly, at the highest concentrations tested: by the metal ions Zn2+, Cu2+, Fe2+ and Fe3+ (approx. 40-80% inhibition); by Rose Bengal and hypochlorite (approx. 80-90% inhibition); and by TGS and dNJ (approx. 50-80%). However, surface-adsorbed Gtfs displayed increased resistance to inhibition by the same metal cations and oxidizing compounds that inhibited them in solution. In contrast, both TGS and dNJ possessed similar inhibition profiles for both surface-bound Gtf and enzyme in solution. These data indicate that the nature of the inhibitor is important, and also whether the Gtf enzyme is in solution or adsorbed to saliva-coated hydroxylapatite.
authors.affiliation: University of Rochester, Center for Oral Biology, NY 14642, USA. David_wunder@urmc.rochester.edu
authors.forename: D
authors.initials: D
authors.lastname: Wunder
authors.forename: W H
authors.initials: WH
authors.lastname: Bowen
mesh_terms: D017485:1-Deoxynojirimycin / Q000494:pharmacology; D000327:Adsorption; D001426:Bacterial Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism*; D002414:Cations, Monovalent / Q000494:pharmacology; D003300:Copper / Q000494:pharmacology; D004269:DNA, Bacterial / Q000378:metabolism; D003741:Dental Deposits / Q000378:metabolism / Q000382:microbiology; D044622:Dental Pellicle; D003773:Dental Plaque / Q000517:prevention & control; D017886:Durapatite / Q000737:chemistry; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005290:Ferric Compounds / Q000494:pharmacology; D005296:Ferrous Compounds / Q000494:pharmacology; D005936:Glucans / Q000494:pharmacology; D005964:Glucosyltransferases / Q000037:antagonists & inhibitors*; D008670:Metals / Q000494:pharmacology*; D016877:Oxidants / Q000494:pharmacology; D012463:Saliva / Q000378:metabolism; D013012:Sorbitol / Q000494:pharmacology; D013295:Streptococcus mutans / Q000187:drug effects / Q000201:enzymology*; D013395:Sucrose / Q000031:analogs & derivatives / Q000494:pharmacology; D013549:Sweetening Agents / Q000494:pharmacology*; D014993:Xylitol / Q000494:pharmacology; D015032:Zinc / Q000494:pharmacology
chemical_list: D001426:Bacterial Proteins; D002414:Cations, Monovalent; D004269:DNA, Bacterial; D004791:Enzyme Inhibitors; D005290:Ferric Compounds; D005296:Ferrous Compounds; D005936:Glucans; D008670:Metals; D016877:Oxidants; D013549:Sweetening Agents; D017485:1-Deoxynojirimycin; D013012:Sorbitol; D013395:Sucrose; D003300:Copper; D017886:Durapatite; C026285:trichlorosucrose; D005964:Glucosyltransferases; D015032:Zinc; D014993:Xylitol