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bioRxiv · 10.1101/605857

In Vitro Potent Activity of ε-poly-L-lysine against Candida albicans and the Underlying Mechanisms

Wei, L.·Yu, T.·Wang, X.·Hou, J.-x.·Wang, C.·Li, K.·Jing, S.·Zhang, X.
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Abstract

ObjectiveThis study aimed to examine the antifungal activity of {varepsilon}-poly-L-lysine ({varepsilon}-PL) against the planktonic cells or biofilms of Candida albicans and explore the underlying mechanism.\n\nMethodsThe 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 {varepsilon}-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 {varepsilon}-PL treatment were measured. The changes in major virulence genes and proteins of C. albicans were detected.\n\nResults{varepsilon}-PL (512 g/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, {varepsilon}-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.\n\nConclusions{varepsilon}-PL exerted a significant antifungal effect on the phytoplankton and biofilm of C. albicans. High concentrations of {varepsilon}-PL significantly inhibited the main mycelium of C. albicans. {varepsilon}-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.\n\nImportanceThe last two decades have seen a growing trend toward the failure of current antifungal drugs attributed to Candida biofilms. 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 to C. albicans.

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Wei, L., Yu, T., Wang, X., Hou, J.-x., Wang, C., Li, K., Jing, S., Zhang, X.. 2019-04-12. In Vitro Potent Activity of ε-poly-L-lysine against Candida albicans and the Underlying Mechanisms. https://doi.org/10.1101/605857

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