| Fungal diseases are gradually becoming important diseases affecting human health,such as the conditional pathogenic fungus Candida albicans,which under certain conditions can lead to human infections,fungal dermatitis,scrotal infection,fungal pneumonia,etc.Most of the current clinical treatment drugs have large side effects and a limited variety of effective antifungal drugs available are yet to be screened and developed.J-15,a soil-derived strain of Bacillus subtilis,and its metabolites(MEs)were found to have potent and broad-spectrum antifungal activity,and the J-15 metabolites were shown to improve the antioxidant capacity of animals(Kunming mice),with the potential to improve animal immunity and be used to treat fungal infections.In this study,we used tail vein injection to construct a mouse model of Candida albicans infection and analyzed the effect of the metabolite on the treatment of Candida albicans infection in mice by gavage administration,and further analyzed the effect of the metabolite on the autoimmunity of mice by physiological and biochemical experiments as well as transcriptomic analysis,laying the foundation for the development of Bacillus subtilis J-15 and its metabolite as a new highly effective and low toxicity antifungal drug.The main results are as follows.(1)J-15 metabolite 90,60,30 mg/kg was used as a dose gradient,fluconazole was used as a control drug and saline was used as a blank control to treat Candida albicans infected mice by gavage for 7 days.The results showed that MEs significantly reduced the mortality of mice in a dose-dependent manner and significantly improved the damage of liver and spleen,total serum antioxidant activity and SOD activity.(2)All mice treated with 90 mg/kg and 30 mg/kg J-15 MEs by gavage for 40 days were healthy and survived,and there was no significant effect on the organ index.The administration of MEs at 90 mg/kg increased the levels of monocytes and platelets in the blood,and significantly increased the levels of Ig A,Ig G,IL-6 and IFN-γ in the blood of mice,which significantly improved the cellular,humoral and non-specific immune functions in mice.(3)Mice treated with 300 mg/kg J-15 MEs by gavage for 20 days were analysed for blood transcriptome and 315 of the 608 differentially expressed genes were up-regulated and 293 were down-regulated compared to the blank group.Among them,immune-related pathways were activated,key protein synthesis genes were significantly up-regulated,such as synthetic T cells,B cells and immunoglobulin-like receptor genes were significantly up-regulated,key protein genes in NF-κB and MAPK pathways were activated,and some important cytokines such as interleukins,transforming growth factors and bone morphogenetic proteins were significantly up-regulated,which is consistent with the results of blood The results were consistent with the results of the blood chemistry index study.In conclusion,it was demonstrated that the metabolite of Bacillus subtilis J-15 could reduce the degree of organ damage in mice infected with Candida albicans and effectively treat Candida albicans infection in mice,and could increase the expression level of immune factors in mice by activating relevant T cells,B cells,immunoglobulin-like receptors and classical immune pathways,and ultimately improve the body’s innate and adaptive immunity.This study provides a basis for the subsequent development of Bacillus subtilis metabolites for the treatment of Candida albicans infections. |
