Abstract
As primary colonizers of the tooth surface, oral streptococci play a crucial role in dental caries development. Numerous natural compounds, including flavonoids, are emerging as promising agents for inhibiting dental biofilm formation without compromising bacterial viability, underscoring their potential in non-bactericidal antibiofilm strategies. This study investigated the effects and mechanism of action of the unmodified plant flavonoid cyanidin on the growth and sucrose-dependent biofilm formation of oral streptococci, with a particular focus on the cariogenic pathogen Streptococcus mutans. At concentrations above 100 µg/mL, cyanidin significantly inhibited biofilm formation by S. mutans without impacting bacterial viability. The flavonoid reduced the biomass of surface-associated bacteria and exopolysaccharides (EPS), particularly by inhibiting water-insoluble glucan (WIG) production mediated by the glucosyltransferases GtfB and GtfC. While cyanidin did not exhibit a bactericidal effect on early colonizer streptococci, such as Streptococcus sanguinis, Streptococcus gordonii, Streptococcus oralis, and Streptococcus mitis, it showed a significant inhibitory effect on bacterial acidogenicity and mixed-species streptococcal biofilms in the presence of S. mutans. Remarkably, cyanidin gradually reduced the proportion of S. mutans in the mixed biofilm, suggesting a selective impact that may promote a more commensal-dominant community by disrupting S. mutans glucan production and biofilm competitiveness. IMPORTANCE: The identification of compounds with potent antibiofilm effects that do not compromise bacterial viability presents a promising strategy for oral health management. By preventing biofilm formation and keeping bacteria in a planktonic state, such agents could enhance bacterial susceptibility to targeted therapies, including probiotics or phage-based treatments. Cyanidin, which exhibits strong antibiofilm activity against oral streptococcal biofilms, reduces bacterial acidogenicity and may promote a more commensal-dominant biofilm in vitro, potentially hindering the maturation of cariogenic biofilms.