根据白色念珠菌在侵袭性念珠菌病中的贡献以及对传统药物耐药性的增加，世界卫生组织已将白色念珠菌于 2022 年列入关键优先组。药物再利用为开发针对病原微生物的替代疗法提供了一种高效、快速且经济高效的解决方案。二盐酸阿力西丁 (AXD) 和六氯酚 (HCP) 分别是 FDA 批准的抗癌药物和防腐药物。在这项研究中，我们展示了 AXD 和 HCP 对白色念珠菌野生型（参考菌株）和临床分离株的抗真菌特性。 AXD 和 HCP 对白色念珠菌的最低抑制浓度 (MIC50) 范围分别为 0.34 至 0.69 µM 和 19.66-24.58 µM。据报道，对于研究中使用的菌株，AXD 的生物膜抑制和根除浓度相对低于 HCP。为了了解 AXD 和 HCP 的抗真菌作用模式，我们进行了进一步的研究，通过研究细胞表面疏水性、粘附性和酵母菌向菌丝转变等毒力特征，这些毒力特征在接触这两种药物后也会降低。暴露于 AXD 和 HCP 后，野生型菌株细胞膜中的麦角甾醇含量上调。对暴露的生物膜的生化分析表明，与未处理的对照生物膜相比，生物膜细胞外基质中碳水化合物、蛋白质和 e-DNA 的含量降低。 AXD 暴露下调了参考菌株中组织侵入酶、磷脂酶的活性。在野生型菌株中，暴露于两种药物后，ROS 水平和抗氧化酶活性均有所升高。经药物处理的生物膜的 FESEM 分析显示生物膜降解。这项研究表明了阿来西定二盐酸盐和六氯酚在白色念珠菌中的抗真菌潜力的作用方式。© 2024。作者获得 Springer-Verlag GmbH 德国（Springer Nature 旗下公司）的独家许可。

Candida albicans has been listed in the critical priority group by the WHO in 2022 depending upon its contribution in invasive candidiasis and increased resistance to conventional drugs. Drug repurposing offers an efficient, rapid, and cost-effective solution to develop alternative therapeutics against pathogenic microbes. Alexidine dihydrochloride (AXD) and hexachlorophene (HCP) are FDA approved anti-cancer and anti-septic drugs, respectively. In this study, we have shown antifungal properties of AXD and HCP against the wild type (reference strain) and clinical isolates of C. albicans. The minimum inhibitory concentrations (MIC50) of AXD and HCP against C. albicans ranged between 0.34 and 0.69 µM and 19.66-24.58 µM, respectively. The biofilm inhibitory and eradication concentration of AXD was reported comparatively lower than that of HCP for the strains used in the study. Further investigations were performed to understand the antifungal mode of action of AXD and HCP by studying virulence features like cell surface hydrophobicity, adhesion, and yeast to hyphae transition, were also reduced upon exposure to both the drugs. Ergosterol content in cell membrane of the wild type strain was upregulated on exposure to AXD and HCP both. Biochemical analyses of the exposed biofilm indicated reduced contents of carbohydrate, protein, and e-DNA in the extracellular matrix of the biofilm when compared to the untreated control biofilm. AXD exposure downregulated activity of tissue invading enzyme, phospholipase in the reference strain. In wild type strain, ROS level, and activities of antioxidant enzymes were found elevated upon exposure to both drugs. FESEM analysis of the drug treated biofilms revealed degraded biofilm. This study has indicated mode of action of antifungal potential of alexidine dihydrochloride and hexachlorophene in C. albicans.© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.