A novel combination therapy effects on Streptococcus mutans biofilms cariogenicity

The development of novel chemotherapeutic agents that disrupt the formation and virulence of dental biofilms is a promising route to prevent or reduce oral infectious diseases such as dental caries. Objectives: The aim of the present study was to examine whether the association of bioactive natural molecules (myricetin and tt-farnesol) enhance the cariostatic properties of fluoride by acting cooperatively on the expression of virulence of Streptococcus mutans. Methods: The effects of topical application of combinations of 1 mM myricetin, 1mM tt-farnesol and fluoride (125 or 250 ppm) on S. mutans UA159 biofilm formation in vitro and development of caries in vivo were determined. The biofilms were subjected to biochemical, structural (confocal laser scanning microscopy) and molecular (real-time PCR) analyses. Sprague-Dawley rats were infected with S. mutans UA159 and treated twice daily with the combinations of agents using our rat model of dental caries. Results: Biofilm dry-weight was significantly reduced by combinations of agents (40-50% reduction compared to control; P<0.05). The biofilms treated with combinations of agents displayed fewer insoluble polysaccharides than did those treated with fluoride alone or vehicle control (P<0.05). The combinations of agents were also effective in reducing the acidogenicity of S. mutans biofilms. The 3-D structural organization of the biofilms treated with the combination of agents was markedly distinct from those treated with fluoride alone or vehicle control. Furthermore, the combinations of agents disrupted the pattern of gtfBCD expression by S. mutans biofilms. The development of dental caries was significantly reduced by the combination therapies (P<0.05). The combination of the natural molecules with lower concentration of fluoride (125 ppm) was particularly effective, and results were comparable with those observed with 250 ppm fluoride (positive control). Conclusions: Results from these studies showed that combination of myricetin, tt-farnesol and fluoride is an alternative and effective anti-caries chemotherapeutic approach. Supported by IADR/GSK Innovation in Oral Care Award.