【Animal Modeling】-Establishment of a mouse model of drug-resistant Candida albicans diffuse infection

  Objective: To establish a mouse model of diffuse infection with drug-resistant Candida albicans and to screen new drugs.

  Method: The clinical fluconazole-resistant Candida albicans CaR was intravenously injected into immunosuppressed ICR mice, and the model was evaluated by clinical symptoms, survival rate, tissue load, histopathology, cytokine analysis and drug treatment.

  Result: CaR-infected mice died 1 day after vaccination. Compared with the clinical drug sensitive strain CaS infection 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 higher mortality was observed earlier in the CaR group CaS group. On the 4th day of infection, Candida was detected in a variety of tissues. Compared with the CaS group, the levels of bacteria in kidney and brain tissues were significantly different. Typical granulomas caused by fungi are the main histopathological features of kidney, brain and heart. The use of flow cytometry to detect renal tissue cytokines leads to significant changes in IL-1α, IL-6, TNF-α, IFN-γ and other cytokines. Compared with the CaS group, IL-1α and IFN-γ were significantly increased, and TNF-α was significantly decreased. CaR and CaS infected mice were treated with 10mg/kg fluconazole, and the mortality was 83.3? 37.5? The difference was significant.

  Conclusion: This study successfully established a mouse model of diffuse infection with drug-resistant Candida albicans. It is expected to become an important tool for the development of new anti-infective drugs.