Key Laboratory for Space Bioscience and Biotechnology, School of Life Sciences, Northwestern Polytechnical University, 127 Youyi West Road, Xi'an, 710072, Shaanxi Province, China.
College of Enology, Northwest A&F University, YangLing, Shaanxi Province, China.
Appl Microbiol Biotechnol. 2021 May;105(9):3759-3770. doi: 10.1007/s00253-021-11296-w. Epub 2021 Apr 26.
Candida albicans (C. albicans) is a fungal pathogen that is difficult to cure clinically due to lack of effective antifungal agents with low toxicity. In this study, iturin, a cyclic peptide having wide antifungal spectrum, was used to synthesize nanosilver particles (AgNPs), and a complex of iturin-AgNPs was formed. The antifungal activity of iturin-AgNPs against C. albicans and its mechanisms were tested in vitro. Iturin-AgNPs were also loaded in chitosan (CS) composite dressing and applied to skin wound healing in mice. As results, iturin-AgNPs showed excellent antifungal activity with the minimum inhibitory concentrations (MIC) of 1.25, 2.5, and 5 μg/mL at C. albicans concentrations of 1×10, 1×10, and 1×10 CFU/mL, respectively. The MIC value still kept at 2.5 μg/mL against C. albicans (10 CFU/mL) after 15 regeneration, showing less induction of drug resistance to the pathogenic fungus. The antifungal mechanisms of iturin-AgNPs against C. albicans were identified as the increase of membrane permeability, damage of cell membrane integrity, and leakage of cellular protein and nucleic acids. No toxicity was found for iturin-AgNPs to HaCaT cells at concentrations of lower than 10 μg/mL. In wound healing application, iturin-AgNP CS composite dressing significantly accelerated the healing of C. albicans infected skin wounds at the early 10 days. In conclusion, iturin-AgNPs were developed as an efficient antifungal agent against C. albicans in vitro and in vivo and showed potential application in wound healing promotion.
白色念珠菌（C. albicans）是一种真菌病原体，由于缺乏毒性低的有效抗真菌药物，临床上难以治愈。在本研究中，使用具有广泛抗真菌谱的环肽伊曲菌素合成纳米银颗粒（AgNPs），形成伊曲菌素-AgNPs 复合物。在体外测试了伊曲菌素-AgNPs 对白色念珠菌的抗真菌活性及其机制。还将伊曲菌素-AgNPs 负载到壳聚糖（CS）复合敷料中，并应用于小鼠皮肤伤口愈合。结果表明，伊曲菌素-AgNPs 对白色念珠菌具有优异的抗真菌活性，在白色念珠菌浓度为 1×10、1×10 和 1×10 CFU/mL 时，其最低抑菌浓度（MIC）分别为 1.25、2.5 和 5 μg/mL。在 15 次再生后，MIC 值仍保持在 2.5 μg/mL，对病原菌的耐药性诱导较小。伊曲菌素-AgNPs 对白色念珠菌的抗真菌机制被鉴定为增加膜通透性、破坏细胞膜完整性以及细胞蛋白和核酸泄漏。在浓度低于 10 μg/mL 时，伊曲菌素-AgNPs 对 HaCaT 细胞没有毒性。在伤口愈合应用中，伊曲菌素-AgNP CS 复合敷料在第 10 天之前显著加速了白色念珠菌感染皮肤伤口的愈合。总之，伊曲菌素-AgNPs 被开发为一种针对白色念珠菌的有效体外和体内抗真菌药物，并显示出在促进伤口愈合方面的潜在应用。
