Plant polyphenols: Antibacterial activity and structural insights

Antimicrobial resistance poses a significant global health challenge, highlighting the urgent need for novel antimicrobial agents. Plant polyphenols, known for their diverse structures and broad-spectrum bioactivities, are promising candidates for novel antimicrobial agents due to their natural origin and low toxicity. In this study, 82 plant polyphenols were evaluated against eight bacterial strains using the agar well diffusion and broth microdilution methods. All 23 tested ellagitannins exhibited antibacterial activity, particularly against Staphylococcus aureus (S. aureus) and β-hemolytic Streptococcus, with minimum inhibitory concentrations ranging from 128 to 512 μg/mL. Significant interspecies differences in susceptibility were observed, with S. aureus and β-hemolytic Streptococcus showing higher susceptibility, while Enterococcus faecalis exhibited considerable resistance. Structure-activity relationship analysis identified key structural determinants: (1) C-O-C-linked gallic acid derivatives in phenolic acids showed superior activity compared to their C-C-linked counterparts; (2) In gallotannins, increasing the number of galloyl groups attached to the glucose core enhanced antibacterial effects; (3) The hexahydroxydiphenoyl group was essential for the antibacterial activity of ellagitannins, and its transformation into the nonahydroxyterphenoyl group significantly broadened the antibacterial spectrum. These findings underscore the potential of plant polyphenols, particularly ellagitannins, as promising antibacterial agents, highlighting the importance of molecular structure in determining antibacterial activity.