Abstract: Objective Based on the Galleria mellonella infection model, the effect of sub-MIC fluconazole on the virulence of Candida glabrata was investigated. Methods Non repetitive Candida glabrata strains clinically isolated from Qinghai Provincial People’s Hospital from April 2021 to October 2022 were collected, and the minimum inhibitory concentration (MIC) of fluconazole against Candida glabrata was determined by ATB method. The virulence of Candida glabrata was tested by the Galleria mellonella infection model, and the success of the model was evaluated by pathological and pathogenic methods. Effects of puncture and different sub-MIC FLUs on healthy Galleria mellonella: the control group did not do any treatment, and the experimental group was divided into three groups, namely PBS group (10 μL PBS), FLU subgroup(inject 10 μL fluconazole solution respectively, making the FLU concentration in the body of infected Galleria mellonella 0.5 mg/kg, 1 mg/kg, 2 mg/kg, 4 mg/kg, 8 mg/kg, and 16 mg/kg) and puncture group (micro syringe puncture but no injection). Use 2.50×10⁶ yeasts /larva infected with Galleria mellonella, after 2 h, the control group was injected with 10 μL PBS, the experimental group was injected with different concentrations of FLU working solution, observing the therapeutic effect on the Galleria mellonella infected by Candida glabrata. Results The MIC of fluconazole to 9 clinically isolated Candida glabrata was 8 mg/L~32 mg/L, and that of Candida glabrata ATCC2001 was 32 mg/L. Yeast-like spores were detected in the pathological section of the intestinal tissue of the Galleria mellonell in the experimental group, and Candida glabra was cultured in the intestinal tissue.No fungus was found in the pathological section and fungal culture of the intestinal tissue in the control group. Puncture could cause damage to the Galleria mellonella, but the mortality was less than 10%. 1/2 MIC fluconazole could improve the survival rate of Candida glabrata infected Galleria mellonella with statistical significance(P<0.05),while 1/4 MIC, 1/8 MIC,1/16 MIC fluconazole had no significant intervention effect on the survival rates of Candida glabrata infected Galleria mellonella compared with PBS and the difference was not statistically significant (P>0.05). Conclusion 1/2 MIC fluconazole had inhibitory effect on the virulence of Candida glabrata, but the concentration below 1/2 MIC had no obvious protective effect.

Key words: Candida glabrata, Galleria mellonella, subinhibitory concentration, fluconazol