The specific degree-of-polymerization of A-type proanthocyanidin oligomers impacts <i>Streptococcus mutans</i> glucan-mediated adhesion and transcriptome responses within biofilms

<div><p>Cranberry A-type proanthocyanidins (PACs) have been recognized for their inhibitory activity against bacterial adhesion and biofilm-derived infections. However, the precise identification of the specific classes of degree-of-polymerization (DP) conferring PACs bioactivity remains a major challenge owing to the complex chemistry of these flavonoids. In this study, chemically characterized cranberries were used in a multistep separation and structure-determination technique to isolate A-type PAC oligomers of defined DP. The influences of PACs on the 3D architecture of biofilms and <i>Streptococcus mutans</i>-transcriptome responses within biofilms were investigated. Treatment regimens that simulated topical exposures experienced clinically (twice-daily, 60 s each) were used over a saliva-coated hydroxyapatite biofilm model. Biofilm accumulation was impaired, while specific genes involved in the adhesion of bacteria, acid stress tolerance, and glycolysis were affected by the topical treatments (<i>vs</i> the vehicle-control). Genes (<i>rmpC</i>, <i>mepA</i>, <i>sdcBB</i>, and <i>gbpC</i>) associated with sucrose-dependent binding of bacteria were repressed by PACs. PACs of DP 4 and particularly DP 8 to 13 were the most effective in disrupting bacterial adhesion to glucan-coated apatitic surface (>85% inhibition <i>vs</i> vehicle control), and gene expression (eg <i>rmpC</i>). This study identified putative molecular targets of A-type cranberry PACs in <i>S. mutans</i> while demonstrating that PAC oligomers with a specific DP may be effective in disrupting the assembly of cariogenic biofilms.</p> </div>