Abstract：
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 D3 (VD3) against various Candida species was investigated. In vitro, the broth microdilution method and solid plate assay confirmed that VD3 inhibited the growth of Candida spp. in a broad-spectrum, dose-dependent manner. VD3 also had a significant antifungal effect on the initiation, development, and maturation phases of biofilm formation in Candida albicans. The mechanism of VD3 action was explored by transcriptomics and reverse transcription quantitative PCR (RT-qPCR) analysis, and showed that VD3 affects ribosome biogenesis, coenzyme metabolism, and carbon metabolism. These results suggested that VD3 may have multitarget effects against C. albicans. In the murine IAC model, VD3 reduced the fungal burden in the liver, kidneys, and small intestine. Further histopathological analysis and quantification of plasma cytokine levels confirmed that VD3 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 VD3 and indicate that VD3 could be an effective therapeutic agent for use in IAC treatment.
摘要：
腹内念珠菌病（IAC）的发病率，具有高发病率和高死亡率的特点，已经成为一个严重的问题。目前市场上抗真菌药物的局限性强调了开发新型抗真菌剂的重要性。在本研究中,研究了维生素D3（VD3）对各种念珠菌的抗真菌活性。体外，肉汤微量稀释法和固体平板试验证实，VD3抑制念珠菌的生长。在广谱中，剂量依赖性方式。VD3也有显著的抗真菌作用，发展,白色念珠菌生物膜形成的成熟期。通过转录组学和逆转录定量PCR(RT-qPCR)分析探讨了VD3的作用机制,并显示VD3影响核糖体生物发生，辅酶代谢，和碳代谢。这些结果表明，VD3可能对白色念珠菌具有多靶点作用。在鼠IAC模型中,VD3减少了肝脏中的真菌负担，肾脏，和小肠。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，VD3治疗可显着降低炎性细胞的浸润以及血浆干扰素（IFN）-γ和肿瘤坏死因子（TNF）-α的水平。一起来看,这些发现提示了VD3的新的抗真菌机制,并表明VD3可能是用于IAC治疗的有效治疗剂.
