Unlocking the antibacterial activity and mechanisms of ε-poly-l-Lysine and perilla combination against Pseudomonas fluorescens: Insights from non-targeted metabolomic analyses

Perilla frutescens extract has been acknowledged for its robust antibacterial properties, while ε -Poly-Lysine ( ε -PL) stands as a naturally occurring food preservative. However, their combined antibacterial activity and mechanisms has not been fully understood. Therefore, the aim of this study was to elucidate the combined antibacterial activity of the ε -PL/Perilla combination against Pseudomonas fluorescens . The findings unveiled a significant antibacterial efficacy of ε -PL and perilla against P. fluorescens , respectively. Upon treatment with ε -PL and perilla, a decline in membrane potential (MP) was observed. These alterations were further accompanied by reductions in nucleic acid content, metabolic activity, and respiratory chain dehydrogenase activity. And by morphological observation, it was found that the cells treated with perilla or ε -PL were severely broken. The metabolomic analysis following treatment with ε -PL and perilla unveiled substantial shifts in a multitude of metabolites. Multivariate statistical analysis showed that ε -PL and perilla hindered nucleotide metabolism and interfered with carbohydrate, amino acid, and lipid metabolism, impacting cell wall biosynthesis, cell membrane structure, and genetic material expression, leading to growth inhibition and bacterial demise. Collectively, these outcomes provide fresh insights into the intricate mechanisms underlying the inhibitory action of ε -PL and perilla against P. fluorescens . • Perilla, ε -PL show synergistic antibacterial effects against P. fluorescens. • Perilla, ε -PL interfere most severely with lipid metabolism in P. fluorescens. • Perilla, ε -PL leads to amino acid depletion and stagnation of cell growth. • Perilla, ε -PL can bind to the phospholipids of the P. fluorescens membrane.