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二十烷对白色念珠菌的体外和体内抗生物膜潜力。

In Vitro and In Vivo Antibiofilm Potential of Eicosane Against Candida albicans.

机构信息

Sathyabama Institute of Science and Technology, Chennai, Tamil Nadu, India.

Department of Biotechnology, Alagappa University, Science Campus, Karaikudi, Tamil Nadu, India.

出版信息

Appl Biochem Biotechnol. 2022 Oct;194(10):4800-4816. doi: 10.1007/s12010-022-03984-8. Epub 2022 Jun 3.

DOI:10.1007/s12010-022-03984-8
PMID:35655004
Abstract

Candida albicans is the most prevalent fungus in humans, producing infections ranging from mucosal to systemic. C. albicans colonizes mucosal surfaces asymptomatically as commensal, but, if the host environment is disrupted, or if the host immune system is compromised, C. albicans can multiply and infect almost all places in the host. The present study was aimed to identify a promising antibiofilm agent against Candida albicans biofilm. Through the molecular docking approach, it was identified that Eicosane was the top hit among the alkanes screened. Furthermore, in vitro analysis revealed that Eicosane at 100 µg/mL was able to inhibit 60% of C. albicans biofilm without inhibiting the growth. Moreover, light microscopic investigation unveiled the significant reduction in the adhesion and colonization of yeast cells to the matrix on Eicosane-treated samples. The CLSM images showing a reduction in biomass and thickness of C. albicans biofilm in the presence of Eicosane were validated using COMSTAT. The results were well corroborated with SEM micrograph in which a pellucid gap between the cells was observed and colonization was considerably reduced. Further from qPCR analysis, the genes responsible for biofilm formation and hyphal growth were found to be downregulated in the presence of Eicosane. Similarly, Eicosane at BIC was able to significantly inhibit the adhesion and colonization of yeast cells on the chorion of the zebrafish embryos. Moreover, the binding ability of Eicosane to ALS3 was revealed through docking and molecular dynamics (MD) simulation studies.

摘要

白色念珠菌是人类最常见的真菌,可引起从黏膜到全身的感染。白色念珠菌作为共生菌无症状地定植在黏膜表面,但如果宿主环境被破坏,或者宿主免疫系统受损,白色念珠菌就会繁殖并感染宿主的几乎所有部位。本研究旨在寻找一种有前途的抗白色念珠菌生物膜的抗菌剂。通过分子对接方法,在筛选出的烷烃中,二十烷被鉴定为最佳命中物。此外,体外分析表明,二十烷在 100μg/ml 时能够抑制 60%的白色念珠菌生物膜形成,而不会抑制其生长。此外,荧光显微镜研究显示,在处理过的样品上,白色念珠菌细胞的黏附和定植到基质的数量显著减少。使用 COMSTAT 验证了在存在二十烷的情况下,CLSM 图像显示生物膜生物量和厚度减少。结果与 SEM 显微照片很好地吻合,在 SEM 照片中观察到细胞之间有明显的空隙,定植明显减少。进一步的 qPCR 分析表明,在存在二十烷的情况下,与生物膜形成和菌丝生长相关的基因表达下调。同样,BIC 的二十烷能够显著抑制酵母细胞在斑马鱼胚胎卵黄囊上的黏附和定植。此外,通过对接和分子动力学(MD)模拟研究揭示了二十烷与 ALS3 的结合能力。

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