Taxifolin Attenuates Bacterial Pathogenicity and Thereby Enhances Antibacterial Efficacy in Clinically Relevant Bacteria

Biofilm formation is an important pathogenic process that contributes to bacterial virulence, persistence, and reduced susceptibility to antimicrobial treatment. Therefore, taxifolin was evaluated as a potential antibiofilm agent. Taxifolin was assessed for its effects on biofilm formation, planktonic growth, antibiotic susceptibility, and the expression of biofilm- and virulence-associated genes. Taxifolin inhibited biofilm formation by Enterococcus faecalis, Enterococcus faecium, Escherichia coli, Streptococcus mutans, Streptococcus sobrinus, Staphylococcus aureus, Pseudomonas aeruginosa, Cutibacterium acnes, and Porphyromonas gingivalis (IC50, 0.065~0.79 µg/mL). In E. faecalis and E. faecium, taxifolin did not substantially affect planktonic growth at 10 µg/mL. Taxifolin enhanced the antibacterial activity of commercially available antibiotics, and downregulated the expression of cytolysin-associated genes (cylR, cylM, and cylLs), quorum-sensing genes (fsrB and fsrC), biofilm-associated genes (gelE, acm, scm, ebpA, ebpB and bps), and the biofilm-associated virulence gene Esp. Taxifolin inhibited biofilm formation, enhanced bacterial susceptibility, and attenuated virulence-associated gene expression, supporting its potential as an adjunctive antibiofilm therapy for the management of biofilm-associated bacterial infections. Further studies are required to define its mechanism of action, activity against established biofilms, pharmacological properties, safety, and efficacy in appropriate in vivo models.