Regulation of Streptococcus mutans biofilm virulence by dietary sugars: Mechanistic basis of sucralose-mediated suppression.
TL;DR
It is shown that sucralose disrupts both EPS structural components and virulence gene regulatory networks in S. mutans, offering novel mechanistic insights into its antibiofilm efficacy against cariogenic biofilms.
Abstract
Streptococcus mutans is a major cariogenic pathogen whose proliferation, acidogenesis, and pathogenicity are strongly impacted by dietary sugars, resulting in dental biofilm-associated illnesses. This study evaluated the effects of sucrose, glucose, and alternative sweeteners (allulose, erythritol, stevia, sucralose, and xylitol) on S. mutans biofilm formation, adhesion, autoaggregation, acidogenicity, metabolic activity, and virulence-related gene expression across different dental surfaces. Sucrose significantly enhanced acid production and biofilm formation, with 3% sucrose resulting in the highest biofilm biomass on both hydroxyapatite (HA) and stainless steel (SS) surfaces. In contrast, alternative sweeteners exhibited variable antibiofilm activity, with sucralose demonstrating the most potent and consistent inhibitory effects across all tested concentrations. Sucralose effectively suppressed sucrose-induced S. mutans biofilm formation, exhibiting dose-dependent antibiofilm activity. Moreover, sucralose significantly reduced bacterial adhesion, the viability of established biofilms, autoaggregation, acid production, intracellular ATP levels, and biofilm structural integrity, as confirmed by confocal laser scanning microscopy (CLSM) and field emission scanning electron microscopy (FE-SEM). Phenol-sulfuric acid analysis further demonstrated a significant reduction in extracellular polymeric substances (EPS) carbohydrate production, while Fourier-transform infrared (FTIR) study demonstrated that sucralose influences EPS composition, namely by lowering polysaccharide-associated components connected to glucan structures. Furthermore, sucralose markedly downregulated key virulence genes involved in biofilm architecture, quorum sensing (QS), and pathogenicity (vicR, gtfC, gbpC, and comX) in a concentration-dependent manner. Notably, this study shows that sucralose disrupts both EPS structural components and virulence gene regulatory networks in S. mutans, offering novel mechanistic insights into its antibiofilm efficacy against cariogenic biofilms.