[Animal modeling] - Establishment of a mouse model of disseminated infection of drug resistant Candida albicans

  Objective: To establish a mouse model of disseminated infection of resistant Candida albicans for screening new drugs.

  Methods: The immunosuppressed ICR mice were injected with fluconazole resistant Candida albicans CaR intravenously. The model was evaluated by clinical symptoms, survival, tissue bacterial load, histopathology, cytokine analysis and drug treatment.

  Results: The CaR infected mice died on the first day after inoculation. Compared with the clinical drug sensitive strain CaS infected group, there was no significant difference in animal mortality during the 16 day observation period (CaR, 90.7%; CaS, 86.2%, P=0.158), but the death rate of the CaR group was faster than that of the CaS group in the early observation period. On the 4th day of infection, candida could be detected in different tissues, and it was found that the bacterial load in kidney and brain tissues was significantly different from that in the CaS group. The typical granuloma caused by fungi is the main histopathological feature of kidney, brain and heart. Detection of cytokines and IL-1 in renal tissue by flow cytometry α、 IL-6、TNF- α、 IFN- γ Significant changes in other cytokines, compared with the CaS group, IL-1 α And IFN- γ Significantly increased, TNF- α Significant decrease. Mice infected with CaR and CaS were treated with 10 mg/kg fluconazole, and the mortality rates were 83.3% and 37.5%, respectively, with significant difference.

  Conclusion: This study successfully established a mouse model of disseminated infection of resistant Candida albicans, which is expected to become an important tool for the development of new anti infective drugs.