【Animal Modeling】-How to establish a mouse model of drug-resistant Candida albicans diffuse infection?

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

  Method: The fluconazole-resistant Candida albicans CaR was injected intravenously into immunosuppressed ICR mice, and the model was evaluated by clinical symptoms, survival rate, tissue load, histopathology, cytokine analysis and drug treatment. Results: The mice infected with CaR died one day after vaccination. 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 in the CaR group. It was observed that the mortality rate was higher than that of the CaS group. On the fourth day of infection, Candida was detected in various tissues. Compared with the CaS group, the levels of bacteria in kidney and brain tissue were significantly different. A typical granuloma caused by a fungus is the main histopathological feature of the kidney, brain, and heart. Using 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, while TNF-α was significantly decreased. Using 10 mg/kg fluconazole to treat CaR and CaS-infected mice, the mortality rate was 83.3% and 37.5%, and 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 agents.