In VitroPotent Activity of ε-poly-L-lysine againstCandida albicansand the Underlying Mechanisms

AbstractObjectiveThis study aimed to examine the antifungal activity of ε-poly-L-lysine (ε-PL) against the planktonic cells or biofilms ofCandida albicansand explore the underlying mechanism.MethodsThe minimal inhibitory concentration, minimum fungal concentration, and sessile minimal inhibitory concentration were estimated. The germ tube formation and yeast-to-hypha transformation ofC. albicansin different media that induced mycelial growth were recorded. The effect of different concentrations of ε-PL on the biofilm formation process and mature biofilm ofC. albicanswas determined. The reactive oxygen species (ROS) and malondialdehyde (MDA) contents ofC. albicansafter ε-PL treatment were measured. The changes in major virulence genes and proteins ofC. albicanswere detected.Resultsε-PL (512 μg/mL) exerted a strong inhibitory effect onC. albicansand biofilms. It blocked the yeast-to-hypha transition and reduced the germ tube formation and germ tube length ofC. albicans. The MDA and ROS contents showed an upward trend, indicating a positive correlation with the concentration. Further, ε-PL inhibited the high expression of virulence genes in oxidative stress induced byC. albicans. The main peak in the mass spectrum ofC. albicanswas found to be clear.Conclusionsε-PL exerted a significant antifungal effect on the phytoplankton and biofilm ofC. albicans. High concentrations of ε-PL significantly inhibited the main mycelium ofC. albicans. ε-PL induced ROS, released cytochrome C, attacked theC. albicanscell membrane to aggravate its lipid oxidation, and inhibited the expression ofC. albicans–associated virulence genes and proteins, thereby exerting a bacteriostatic effect.ImportanceThe last two decades have seen a growing trend toward the failure of current antifungal drugs attributed toCandidabiofilms. Under appropriate conditions, adherence and colonization of planktonic cells on host tissues and medical devices initiate multicellular organization called biofilm, which is an organized heterogeneous mixture of yeast, hyphae, and pseudohyphal forms embedded in a complex extracellular matrix. Compared with the planktonic cells, biofilms show high resistance to a wide variety of antifungal agents and tolerance to harsh environments and host immune system. Moreover, the development of antifungal drugs is costly, long-term, and difficult. Thus, researchers turned their attention to natural antibacterial peptides, hoping to find an effective antifungal substance or enhance the sensitivity of the existing antifungal drugs toC. albicans.