Antifungal activity and mechanism of action of dichloromethane extract fraction A from Streptomyces libani against Aspergillus fumigatus
Antifungal activity and mechanism of action of dichloromethane extract fraction A from Streptomyces libani against Aspergillus fumigatus
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DOI：
10.1111/jam.15040
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发表时间：
2021-03-09
影响因子：
4
通讯作者：
Razzaghi-Abyaneh, M.
中科院分区：
文献类型：
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作者：
Azish, M.;Shams-Ghahfarokhi, M.;Razzaghi-Abyaneh, M.
目的研究二氯甲烷链霉菌提取物A(DCEFA)对烟曲霉菌的抑菌作用机制及其对宿主细胞的毒性作用。方法与结果采用自传法从荔枝链霉菌中分离纯化DCEFA，并显示出较强的抗真菌活性。结合电子显微镜、细胞通透性测定、总氧化剂状态(TOS)测定、细胞毒性测定和溶血活性测定确定DCEFA的靶点。烟曲霉菌暴露于DCEFA后，细胞膜结构受到破坏，细胞物质、钾离子和TOS的释放增加。DCEFA与麦角甾醇结合，但不影响真菌细胞壁和麦角甾醇含量。DCEFA对红细胞没有明显的溶血活性，对HEK-293细胞也没有明显的毒性。结论DCEFA可能通过靶向真菌细胞膜，导致钾离子和其他细胞成分的渗漏，TOS的产生，最终细胞死亡，从而抑制烟曲霉菌的生长。
Aims This study aimed to investigate the mechanism of antifungal action of Streptomyces libani dichloromethane extract fraction A (DCEFA) against Aspergillus fumigatus and the host cytotoxicity.Methods and Results DCEFA was purified from S. libani by autobiography and showed strong antifungal activity against A. fumigatus. A combination of electron microscopy, cell permeability assays, total oxidant status (TOS) assay, cell cytotoxicity assay and haemolysis activity was carried out to determine the target site of DCEFA. Exposure of A. fumigatus to DCEFA caused the damage to membranous cellular structures and increased release of cellular materials, potassium ions and TOS production. DCEFA was bound to ergosterol but did not affect fungal cell wall and ergosterol content. DCEFA did not show any obvious haemolytic activity for RBCs and toxicity against HEK-293 cell line.Conclusions DCEFA may inhibit A. fumigatus growth by targeting fungal cell membrane which results in the leakage of potassium ions and other cellular components, TOS production and final cell death.Significance and Impact of the Study DCEFA of S. libani could be considered as a potential source of novel antifungals which may be useful for drug development against A. fumigatus as a life-threatening human pathogen.