Metabolomic Analysis of Antimicrobial Mechanisms of ε‑Poly‑l‑lysine on Saccharomyces cerevisiae

ε-Poly-l-lysine (ε-PL), a naturally occurring amino acid homopolymer, has been widely used as a food preservative. However, its antimicrobial mechanism has not been fully understood. This study investigated the antimicrobial mode of action of ε-PL on a yeast, Saccharomyces cerevisiae. When treated with ε-PL at the concentration of 500 μg/mL, cell mortality was close to 100% and the phospholipid bilayer curvature, pores, and micelles on the surface of S. cerevisiae were clearly observed by scanning electron microscopy (SEM). At the level of 200 μg/mL, ε-PL significantly inhibited the cell growth of S. cerevisiae. When treated with 50 μg/mL ε-PL, the yeast cell was able to grow but the cell cycle was prolonged. A significant increase in cell membrane permeability was induced by ε-PL at higher concentrations. Metabolomics analysis revealed that the ε-PL stress led to the inhibition of primary metabolic pathways through the suppression of the tricarboxylic acid cycle and glycolysis. It is therefore proposed that the microbiostatic effect of ε-PL at lower levels on S. cerevisiae is achieved by inducing intracellular metabolic imbalance via disruption of cell membrane functions. Moreover, the results suggested that the antimicrobial mechanism of ε-PL on S. cerevisiae can in fact change from microbiostatic to microbicidal when the concentration of ε-PL increased, and the mechanisms of these two modes of action were completely different.