Department of Pathogenic Biology and Immunology, College of Integrated Chinese and Western Medicine, (College of Life Science), Anhui University of Chinese Medicine, No. 350 Longzihu Road, Xinzhan District, Hefei, 230012, China.
Institute of Integrated Traditional Chinese and Western Medicine, Anhui University of Chinese Medicine, Hefei, China.
Arch Microbiol. 2024 Sep 16;206(10):404. doi: 10.1007/s00203-024-04136-8.
The emergence of the "super fungus" Candida auris poses a significant threat to human health, given its multidrug resistance and high mortality rates. Therefore, developing a new antifungal strategy is necessary. Our previous research showed that Baicalein (BE), a key bioactive compound from the dried root of the perennial herb Scutellaria baicalensis Georgi, has strong fungistatic properties against C. auris. Nevertheless, the antifungal activity of BE against C. auris and its mechanism of action requires further investigation. In this study, we explored how BE affects this fungus using various techniques, including scanning electron microscopy (SEM), Annexin V-FITC apoptosis detection, CaspACE FITC-VAD-FMK In Situ Marker, reactive oxygen species (ROS) assay, singlet oxygen sensor green (SOSG) fluorescent probe, enhanced mitochondrial membrane potential (MMP) assay with JC-1, DAPI staining, TUNEL assay and reverse transcription-quantitative polymerase chain reaction (RT-qPCR). Our findings revealed that BE induced several apoptotic features, including phosphatidylserine (PS) externalization, metacaspase activation, nuclear condensation and DNA fragmentation. BE also increased intracellular ROS levels and altered mitochondrial functions. Additionally, transcriptomic analysis and RT-qPCR validation indicated that BE may induce apoptosis in C. auris by affecting ribosome-related pathways, suggesting that ribosomes could be new targets for antifungal agents, in addition to cell walls, membranes, and DNA. This study emphasizes the antifungal activity and mechanism of BE against C. auris, offering a promising treatment strategy for C. auris infection.
耳念珠菌的出现对人类健康构成了重大威胁，因为它具有多药耐药性和高死亡率。因此，开发新的抗真菌策略是必要的。我们之前的研究表明，黄芩素（BE），一种来自多年生草本植物黄芩的干根的关键生物活性化合物，对耳念珠菌具有很强的抑菌作用。然而，BE 对耳念珠菌的抗真菌活性及其作用机制需要进一步研究。在这项研究中，我们使用各种技术探索了 BE 如何影响这种真菌，包括扫描电子显微镜（SEM）、膜联蛋白 V-FITC 凋亡检测、CaspACE FITC-VAD-FMK 原位标记、活性氧（ROS）测定、单线态氧传感器绿（SOSG）荧光探针、增强型线粒体膜电位（MMP）测定用 JC-1、DAPI 染色、TUNEL 测定和逆转录定量聚合酶链反应（RT-qPCR）。我们的研究结果表明，BE 诱导了几种凋亡特征，包括磷脂酰丝氨酸（PS）外翻、效应蛋白酶激活、核浓缩和 DNA 片段化。BE 还增加了细胞内 ROS 水平并改变了线粒体功能。此外，转录组分析和 RT-qPCR 验证表明，BE 可能通过影响核糖体相关途径诱导耳念珠菌凋亡，这表明核糖体除了细胞壁、膜和 DNA 外，也可能成为抗真菌药物的新靶点。这项研究强调了 BE 对耳念珠菌的抗真菌活性和机制，为耳念珠菌感染提供了一种有前途的治疗策略。
