Objective: This study aimed to examine the antifungal activity of e-poly-L-lysine (e-PL) against the planktonic cells or biofilms of Candida albicans and explore the underlying mechanism. Methods: The minimal inhibitory concentration, minimum fungal concentration, and sessile minimal inhibitory concentration were estimated. The germ tube formation and yeast-to-hypha transformation of C. albicans in different media that induced mycelial growth were recorded. The effect of different concentrations of e-PL on the biofilm formation process and mature biofilm of C. albicans was determined. The reactive oxygen species (ROS) and malondialdehyde (MDA) contents of C. albicans after e-PL treatment were measured. The changes in major virulence genes and proteins of C. albicans were detected. Results: e-PL (512 mg/mL) exerted a strong inhibitory effect on C. albicans and biofilms. It blocked the yeast-to-hypha transition and reduced the germ tube formation and germ tube length of C. albicans. The MDA and ROS contents showed an upward trend, indicating a positive correlation with the concentration. Further, e-PL inhibited the high expression of virulence genes in oxidative stress induced by C. albicans. The main peak in the mass spectrum of C. albicans was found to be clear. Conclusions: e-PL exerted a significant antifungal effect on the phytoplankton and biofilm of C. albicans. High concentrations of e-PL significantly inhibited the main mycelium of C. albicans. e-PL induced ROS, released cytochrome C, attacked the C. albicans cell membrane to aggravate its lipid oxidation, and inhibited the expression of C. albicans-associated virulence genes and proteins, thereby exerting a bacteriostatic effect.
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