Li Ying, Shan Mingzhu, Li Shihui, Wang Yuechen, Yang Huan, Chen Ying, Gu Bing, Zhu Zuobin
Medical Technology School of Xuzhou Medical University, Xuzhou Key Laboratory of Laboratory Diagnostics, Xuzhou 221004, China.
Department of Genetics, Xuzhou Medical University, Xuzhou 214200, China.
Ann Transl Med. 2020 Mar;8(5):175. doi: 10.21037/atm.2020.01.124.
Candidiasis has long been a threat to human health, but cytotoxicity and resistance always block the usefulness of antifungal agents. The ability to switch between yeast and hypha is one of the most discussed virulence trait attributes of the human pathogenic fungus . The morphological transition provides a novel target for developing antifungal drugs. The aim of the present study was to explore the activity and mechanism of teasaponin (TS), a generally regarded as safe natural product, in inhibiting filamentation of , hoping to provide an experimental basis for its clinical application.
The effect of TS on filamentation and biofilm formation of was evaluated by XTT reduction assay and microscopy. The level of intracellular cAMP was measured to further explore the underlying mechanism. In addition, cytotoxicity of TS was evaluated by using MTT assay and model . The potential of TS-resistance induction was tested by a serial passage experiment.
TS displayed a moderate antifungal activity against the wild type, efflux pump mutant and multi-resistance strains, and could effectively retard filamentation and biofilm formation with a low MIC value. Further mechanism investigation revealed that the reduced cAMP level inhibited filamentation and biofilm formation. In addition, TS showed no significant cytotoxicity or , and had little potential to develop resistance during long-time induction.
Our work evaluated the antifungal activity of TS against filamentation and biofilms formation of and disclosed the underlying mechanism, which might provide useful clues for the potential clinical application of TS in fighting clinical fungal infections by targeting the virulence factors.
念珠菌病长期以来一直威胁着人类健康，但细胞毒性和耐药性始终阻碍着抗真菌药物的有效性。在酵母和菌丝之间转换的能力是人类致病真菌最受关注的毒力特征属性之一。形态转变为开发抗真菌药物提供了一个新靶点。本研究旨在探讨茶皂素（TS）（一种普遍认为安全的天然产物）抑制丝状化的活性及机制，希望为其临床应用提供实验依据。
通过XTT还原试验和显微镜观察评估TS对丝状化和生物膜形成的影响。测量细胞内cAMP水平以进一步探究潜在机制。此外，使用MTT试验和 模型评估TS的细胞毒性。通过连续传代实验测试诱导TS耐药的可能性。
TS对野生型、外排泵突变体和多重耐药 菌株表现出中等抗真菌活性，且能以低MIC值有效延缓丝状化和生物膜形成。进一步的机制研究表明，cAMP水平降低抑制了丝状化和生物膜形成。此外，TS对 或 无明显细胞毒性，且在长时间诱导过程中产生耐药的可能性很小。
我们的工作评估了TS对丝状化和生物膜形成的抗真菌活性，并揭示了潜在机制，这可能为TS通过靶向毒力因子对抗临床真菌感染的潜在临床应用提供有用线索。
