The Central Laboratory, Peking University School and Hospital of Stomatology, Beijing, 100081, China; Shanxi Medical University School and Hospital of Stomatology, Taiyuan, 030001, China.
Shanxi Medical University School and Hospital of Stomatology, Taiyuan, 030001, China.
J Infect Chemother. 2021 May;27(5):696-701. doi: 10.1016/j.jiac.2020.12.012. Epub 2020 Dec 23.
Candida albicans and Candida auris strains are common causative species of Candidiasis. The limited number of antifungal drugs and the current situation of resistance to existing antifungals force us to search for new antifungal alternatives.
In this work, primary screening of small molecule libraries (Metabolism Compound Library and Epigenetics Compound Library) consisting of 584 compounds against Candida albicans SC5314 was performed. The dose-response assays, XTT assays, scanning electron microscopy and confocal laser scanning microscopy were used to confirm the antifungal activities of the selected compounds against Candida strains.
Through the primary screening, we identified five compounds (U73122, disulfiram, BSK805, BIX01294, and GSKJ4) that inhibited strains growth ≥ 80% for dose-response assays. Disulfiram was identified as the most potent repositionable antifungal drug with 50% growth inhibition detected at a concentration as low as 1 mg/L. The further results showed the antifungal activity of disulfiram against biofilm formation of Candida strains with a 50% minimum inhibitory concentration ranging from 32 to 128 mg/L. Further observations by scanning electron microscopy and confocal laser scanning microscopy confirmed the destruction of biofilm architecture and the change of biofilm morphology after being exposed to disulfiram.
The study indicated the potential clinical application of disulfiram as a promising antifungal drug against candidiasis.
白色念珠菌和耳念珠菌是念珠菌病的常见病原体。抗真菌药物的数量有限，以及现有抗真菌药物的耐药现状迫使我们寻找新的抗真菌替代品。
在这项工作中，对包含 584 种化合物的小分子文库（代谢化合物文库和表观遗传学化合物文库）对白色念珠菌 SC5314 进行了初步筛选。采用剂量反应试验、XTT 试验、扫描电子显微镜和共聚焦激光扫描显微镜来确认所选化合物对念珠菌株的抗真菌活性。
通过初步筛选，我们确定了五种化合物（U73122、双硫仑、BSK805、BIX01294 和 GSKJ4）对剂量反应试验的菌株生长抑制率≥80%。双硫仑被确定为最有效的可重定位抗真菌药物，其 50%生长抑制浓度低至 1mg/L。进一步的结果表明，双硫仑对念珠菌生物膜形成具有抗真菌活性，最低抑菌浓度为 32 至 128mg/L。扫描电子显微镜和共聚焦激光扫描显微镜的进一步观察证实了双硫仑暴露后生物膜结构的破坏和生物膜形态的变化。
该研究表明双硫仑作为一种有前途的抗真菌药物，具有治疗念珠菌病的潜在临床应用价值。
