Dual Mode of Anti-Biofilm Action of G3 against Streptococcus mutans

Oral biofilms, formed by multiple microorganisms and their extracellular polymeric substances, seriously affect people's life. The emergence of the resistance of biofilms to conventional antibiotics and their side effects on the oral cavity have posed a great challenge in the treatment of dental diseases. Recently, antimicrobial peptides have been recognized as promising alternatives to conventional antibiotics due to their broad antibacterial spectrum, high antibacterial activity, and specific mechanism. However, the research of their anti-biofilm behaviors is still in its infancy, and the underlying mechanism remains unclear. In this study, we investigated the anti-biofilm activities of a designed helical peptide (G3) against Streptococcus mutans (S. mutans), one of the primary causative pathogens of caries. The results indicated that G3 inhibited S. mutans biofilm formation by interfering with different stages of biofilm development. At the initial stage, G3 inhibited the bacterial adhesion by decreasing the bacterial surface charges, hydrophobicity, membrane integrity, and adhesion-related gene transcription. At the later stage, G3 interacted with extracellular DNA to destabilize the 3D architecture of mature biofilms and thus dispersed them. The high activity of G3 against S. mutans biofilms, along with its specific modes of action, endows it great application potential in preventing and treating dental plaque diseases.