Department of Biotechnology, Graphic Era (Deemed to be University), Dehradun, 248001, Uttarakhand, India.
Department of Biosciences and Bioengineering, Indian Institute of Technology Roorkee, Roorkee, Uttarakhand, 247667, India.
Arch Microbiol. 2024 Aug 20;206(9):383. doi: 10.1007/s00203-024-04103-3.
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 (MIC) 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.
白色念珠菌已被世界卫生组织列为 2022 年的重点优先事项，这主要是因为它会导致侵袭性念珠菌病，并对常规药物产生抗药性。药物再利用为开发针对致病微生物的替代疗法提供了一种高效、快速且具有成本效益的解决方案。盐酸阿霉素（AXD）和六氯酚（HCP）分别是 FDA 批准的抗癌和抗菌药物。在这项研究中，我们已经证明了 AXD 和 HCP 对白色念珠菌野生型（参考株）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菌浓度（MIC）分别在 0.34 到 0.69 µM 和 19.66 到 24.58 µM 之间。与研究中使用的菌株相比，AXD 的生物膜抑制和根除浓度明显低于 HCP。进一步的研究旨在通过研究细胞表面疏水性、黏附性和酵母向菌丝转变等毒力特征，来了解 AXD 和 HCP 的抗真菌作用机制，结果显示，这两种药物都降低了这些特征。暴露于 AXD 和 HCP 后，野生型菌株的细胞膜中麦角固醇含量增加。对暴露于药物的生物膜进行生化分析表明，与未经处理的对照生物膜相比，生物膜的细胞外基质中的碳水化合物、蛋白质和 e-DNA 含量减少。AXD 暴露降低了参考株组织侵袭酶磷脂酶的活性。在野生型菌株中，发现 ROS 水平和抗氧化酶活性在暴露于两种药物后升高。经药物处理的生物膜的 FESEM 分析显示生物膜降解。这项研究表明了盐酸阿霉素和六氯酚在白色念珠菌中的抗真菌作用机制。
