Tetrandrine eliminates fluconazole tolerance in Candida albicans by inhibiting efflux pump
Objective This study aimed to investigate how tetrandrine affects the fluconazole tolerance of Candida albicans and its underlying mechanisms.Methods Candida albicans reference strain SC5314 was used in this study.The susceptibil-ity of SC5314 to fluconazole in the presence of tetrandrine was evaluated using the disk diffusion assay.The impact of tetran-drine on the expression of efflux pump genes was assessed by RT-PCR.The main efflux pump genes CDR1,CDR2,and MDR1 were individually knocked out to study their influence on fluconazole tolerance.Additionally,the effect of the efflux pump inhibitor verapamil on fluconazole tolerance was also evaluated.Results Tetrandrine could eliminate the fluconazole tolerance of C.albicans.Tetrandrine alone did not significantly affect the expression of efflux pump genes,but when used in combination with fluconazole,it significantly inhibited the expression of the efflux pump gene CDR1.Knocking out CDR1 or adding the efflux pump inhibitor verapamil effectively eliminated tolerance in tolerant isolates.Conclusion Tetrandrine elim-inates the fluconazole tolerance of C.albicans by suppressing the expression of the efflux pump gene CDR1.This study pro-vides important clues for further exploring drug synergies to combat fluconazole tolerance in C.albicans.
万方数据
维普
