Antifungal activity of vitamin D3 against Candida albicans in vitro and in vivo

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 histo-pathological 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)-gamma and tumor necrosis factor (TNF)-alpha. 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.