Inhibitory effects of 7-epiclusianone on glucan synthesis, acidogenicity and biofilm formation by Streptococcus mutans

Abstract

The aim of this study was to examine the effects of 7-epiclusianone, a new prenylated benzophenone isolated from the plant Rheedia gardneriana, on some of the virulence properties of Streptococcus mutans associated with biofilm development and acidogenicity. The synthesis of glucans by glucosyltransferases B (GTF B) and C (GTF C) was markedly reduced by 7-epiclusianone showing more than 80% inhibition of enzymatic activity at a concentration of 100 microg mL(-1). Double-reciprocal analysis (Lineweaver-Burk plots) revealed that the inhibition of GTF B activity was noncompetitive (mixed) while GTF C was inhibited uncompetitively. The glycolytic pH drop by S. mutans cells was also disrupted by 7-epiclusianone without affecting the bacterial viability, an effect that can be attributed, in part, to inhibition of F-ATPase activity (61.1+/-3.0% inhibition at 100 microg mL(-1)). Furthermore, topical applications (1-min exposure, twice daily) of 7-epiclusianone (at 250 microg mL(-1)) disrupted biofilm formation and physiology. The biomass (dry-weight), extracellular insoluble polysaccharide concentration and acidogenicity of the biofilms were significantly reduced by the test agent (P<0.05). The data show that 7-epiclusianone disrupts the extracellular and intracellular sugar metabolism of S. mutans, and holds promise as a novel, naturally occurring compound to prevent biofilm-related oral diseases.

Influence of Cranberry Proanthocyanidins on Formation of Biofilms by <i>Streptococcus mutans</i> on Saliva-Coated Apatitic Surface and on Dental Caries Development in vivo

“…For example, PAC from other fruits that lack A-type linkage are without effect on Gtf enzymes, whereas PAC larger than trimers (DP of 1 3) are more effective Gtf inhibitors than monomers and dimers [Yanagida et al, 2000;Osawa et al, 2001]. It is likely that PAC are noncompetitive inhibitors based on our previous studies with other polyphenolic compounds [Koo et al, 2002;Murata et al, 2008]. PAC have shown to bind proteins, forming protein-polyphenol complexes [Haslam, 1996] which can affect the enzyme activity by irreversibly binding to the catalytic domain, glucan-binding domain and/or other sites once complexed.…”

A New Small Molecule Specifically Inhibits the Cariogenic Bacterium Streptococcus mutans in Multispecies Biofilms

“…These substances can regulate the activities of surface-anchored virulence factors glucosyltransferase and fructosyltransferase (5,7,9,14,34). Numerous small molecules, including anthraquinones, apigenin, tt-farnesol, chitosan, and 7-epiclusianone, have been characterized and shown to have antibiofilm activity toward S. mutans (2,17,25,26). However, none of them were reported to possess selectivity against S. mutans biofilms.…”

Halistanol sulfate A and rodriguesines A and B are antimicrobial and antibiofilm agents against the cariogenic bacterium Streptococcus mutans

“…Additionally, natural product-based treatments, such as propolis and plant extracts, have been successfully used against dental caries (Koo et al, 2000(Koo et al, , 2006Galvão et al, 2012). Examples of anticariogenic natural products include anthraquinones, apigenin, tt-farnesol, chitosan, 7-epiclusianone, 2-aminoimidazole and 2-aminobenzimidazole, several of which have shown antibiofilm activity against Streptococcus mutans (Koo et al, 2003;Coenye et al, 2007;Murata et al, 2008;Pasquantonio et al, 2008;Liu et al, 2011). However, very few natural products isolated from marine organisms have been evaluated as inhibitors of bacterial oral pathogens.…”