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Kalopanaxsaponin A induces reactive oxygen species mediated mitochondrial dysfunction and cell membrane destruction in Candida albicans
PLOS ONE ( IF 3.7 ) Pub Date : 2020-11-30 , DOI: 10.1371/journal.pone.0243066
Ying Li , Mingzhu Shan , Yao Zhu , Huankai Yao , Hongchun Li , Bing Gu , Zuobin Zhu

Candidiasis causes high morbidity and mortality among immunocompromised patients. Antifungal drug resistance and cytotoxicity highlight the need of effective antifungal therapeutics. In this study, we found that kalopanaxsaponin A (KPA), a triterpenoid saponin natural product, could inhibit the proliferation of various Candida species, and exerted a fungicidal effect against C. albicans. To further explore its antifungal action mode, spectrofluorophotometer, fluorescence microscopy and transmission electron microscopy were performed, showing that KPA treatment induced the accumulation of intracellular reactive oxygen species (ROS), resulting in mitochondrial dysfunction. Meanwhile, KPA treatment also broke down the membrane barrier of C. albicans causing the leakage of intracellular trehalose, the entrance of extracellular impermeable substance and the decrease of ergosterol content. Both ROS accumulation and membrane destruction contributed to the death of C. albicans cells. Our work preliminarily elucidated the potential mechanisms of KPA against C. albicans on a cellular level, and might provide a potential option for the treatment of clinical candidiasis.



中文翻译:

Kalopanaxsaponin A诱导白色念珠菌介导的活性氧介导的线粒体功能障碍和细胞膜破坏

念珠菌病在免疫功能低下的患者中引起较高的发病率和死亡率。抗真菌药物的耐药性和细胞毒性凸显了对有效抗真菌药物的需求。在这项研究中,我们发现三萜皂苷天然产物kalopanaxsaponin A(KPA)可以抑制各种念珠菌的增殖,并对C发挥杀菌作用。白色的。为了进一步探索其抗真菌作用模式,进行了分光光度计,荧光显微镜和透射电子显微镜的研究,结果表明,KPA处理诱导了细胞内活性氧(ROS)的积累,从而导致线粒体功能障碍。同时,KPA处理也打破了C的膜屏障白色念珠菌引起细胞内海藻糖的泄漏,细胞外不可渗透物质的进入和麦角固醇含量的降低。ROS积累和膜破坏均导致C的死亡。白色的细胞。我们的工作初步阐明了KPA对抗C的潜在机制。白细胞在细胞水平上,可能为临床念珠菌病的治疗提供潜在的选择。

更新日期:2020-12-01
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