The Platform of Molecular Biotechnology, Public Center of Experimental Technology, School of Basic Medical Sciences, Southwest Medical University, Luzhou 646000, People's Republic of China.
Huangdao District of Traditional Chinese Medicine, Qingdao 266500, China.
Microbiol Res. 2022 Dec;265:127200. doi: 10.1016/j.micres.2022.127200. Epub 2022 Sep 20.
The incidence of intra-abdominal candidiasis (IAC), characterized by high morbidity and mortality, has become a serious concern. The limitations of current antifungal drugs on the market underscores the importance of the development of novel antifungal agents. In the present study, the antifungal activity of vitamin D (VD) against various Candida species was investigated. In vitro, the broth microdilution method and solid plate assay confirmed that VD inhibited the growth of Candida spp. in a broad-spectrum, dose-dependent manner. VD also had a significant antifungal effect on the initiation, development, and maturation phases of biofilm formation in Candida albicans. The mechanism of VD action was explored by transcriptomics and reverse transcription quantitative PCR (RT-qPCR) analysis, and showed that VD affects ribosome biogenesis, coenzyme metabolism, and carbon metabolism. These results suggested that VD may have multitarget effects against C. albicans. In the murine IAC model, VD reduced the fungal burden in the liver, kidneys, and small intestine. Further histopathological analysis and quantification of plasma cytokine levels confirmed that VD treatment significantly decreased the infiltration of inflammatory cells and the levels of plasma interferon (IFN)-γ and tumor necrosis factor (TNF)-α. Taken together, these findings suggest a new antifungal mechanism for VD and indicate that VD could be an effective therapeutic agent for use in IAC treatment.
腹腔内念珠菌病（IAC）的发病率很高，死亡率也很高，这已成为一个严重的问题。目前市场上抗真菌药物的局限性突显了开发新型抗真菌药物的重要性。本研究探讨了维生素 D（VD）对各种念珠菌属的抗真菌活性。在体外，肉汤微量稀释法和固体平板测定法证实 VD 以广谱、剂量依赖性方式抑制念珠菌属的生长。VD 还对白色念珠菌生物膜形成的起始、发展和成熟阶段具有显著的抗真菌作用。通过转录组学和逆转录定量 PCR（RT-qPCR）分析探讨了 VD 的作用机制，结果表明 VD 影响核糖体生物发生、辅酶代谢和碳代谢。这些结果表明 VD 可能对白色念珠菌具有多靶作用。在 IAC 小鼠模型中，VD 降低了肝脏、肾脏和小肠中的真菌负荷。进一步的组织病理学分析和血浆细胞因子水平的定量证实，VD 治疗显著减少了炎症细胞的浸润和血浆干扰素（IFN）-γ和肿瘤坏死因子（TNF）-α的水平。综上所述，这些发现为 VD 提供了一种新的抗真菌机制，并表明 VD 可能是治疗 IAC 的有效治疗药物。
