Can Li, Jun Wang, Hui Wu, Long Zang, Wei Qiu, Wenfan Wei, Tianming Wang, Changzhong Wang
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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 <i>C. auris</i> 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 <i>C. auris</i>, offering a promising treatment strategy for <i>C. auris</i> infection.</p><h3>Graphical Abstract</h3><div><figure><div><div><picture><source><img></source></picture></div><div><p>Schematic representation of this study. Baicalein (BE) triggers apoptosis in <i>Candida auris</i> by affecting ribosome-related pathways. 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引用次数: 0
摘要
超级真菌 "白色念珠菌的出现对人类健康构成了重大威胁,因为它具有多重抗药性和高死亡率。因此,有必要开发一种新的抗真菌策略。我们之前的研究表明,从多年生草本植物黄芩(Scutellaria baicalensis Georgi)的干燥根中提取的一种关键生物活性化合物--黄芩素(Beicalein,BE)对白色念珠菌具有很强的抗真菌作用。然而,BE 的抗真菌活性及其作用机制还需要进一步研究。在这项研究中,我们使用了多种技术,包括扫描电子显微镜(SEM)、Annexin V-FITC细胞凋亡检测、CaspACE FITC-VAD-FMK原位标记、活性氧(ROS)检测等,探讨了BE如何影响这种真菌、单线态氧传感器绿(SOSG)荧光探针、JC-1 线粒体膜电位(MMP)增强检测、DAPI 染色、TUNEL 检测和反转录定量聚合酶链反应(RT-qPCR)。我们的研究结果表明,BE 可诱导多种凋亡特征,包括磷脂酰丝氨酸(PS)外化、元天冬酶活化、核凝聚和 DNA 断裂。BE还增加了细胞内ROS水平,改变了线粒体功能。此外,转录组分析和 RT-qPCR 验证表明,BE 可能会通过影响核糖体相关途径诱导 C. auris 的细胞凋亡,这表明除了细胞壁、细胞膜和 DNA 外,核糖体也可能成为抗真菌药物的新靶点。这项研究强调了BE的抗真菌活性和抗蛔虫机制,为治疗蛔虫感染提供了一种前景广阔的治疗策略。
Baicalein induces apoptosis by targeting ribosomes in Candida auris
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.
期刊介绍:
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