Mechanistic Insights into the Inhibition of Streptococcus mutans Biofilms by Chlorogenic Acid

Based on the preliminary screening of the potential active components that inhibit the biofilm of Streptococcus mutans from the extract of Lonicera japonicaflos (LJF), we identified chlorogenic acid (CA), a polyphenol compound, as a potential active component against S. mutans biofilms. To elucidate its molecular mechanism, we performed integrated transcriptomic and metabolomic analyses. CA treatment markedly altered biofilm morphology without affecting bacterial viability, primarily through decreased glucan production, a key reason for antibiofilm formation. Multiomics integration revealed that the inhibitory effect of CA was mainly associated with carbohydrate and amino acid metabolism, particularly sucrose and pyruvate pathways. Further biochemical validation identified glycosyltransferases (Gtfs) and the sensor kinase VicK as direct CA-binding targets. Structural modeling demonstrated stable hydrogen-bonding interactions between CA and residues within the catalytic domains of both proteins, supporting a mechanism in which CA competitively disrupts substrate utilization and impairs glucan biosynthesis. Together, these results provide mechanistic insight into how CA inhibits S. mutans biofilms and suggest its potential application for studying biofilm regulation.