粉防己碱通过抑制外排泵消除白念珠菌对氟康唑的耐受  

Tetrandrine eliminates fluconazole tolerance in Candida albicans by inhibiting efflux pump

作　　者：丁敏露 杨晓潓 蔡同凯 贾成林 曹永兵 DING Minlu;YANG Xiaohui;CAI Tongkai;JIA Chenglin;CAO Yongbing(Institute of Vascular Anomalies,Shanghai TCM-Integrated Hospital,Shanghai University of Traditional Chinese Medicine,Shanghai 200082,China)

机构地区：[1]上海中医药大学附属上海市中西医结合医院脉管病研究所,上海200082

出　　处：《中国真菌学杂志》2024年第6期585-590,共6页Chinese Journal of Mycology

基　　金：国家自然科学基金面上项目(81872910);上海市基础研究重点项目(19JC1414900)。

摘　　要：目的研究粉防己碱影响白念珠菌对氟康唑的耐受性及其潜在机制。方法选择白念珠菌标准菌株SC5314,采用纸片扩散法测试粉防己碱对其氟康唑耐受性的影响;通过RT-PCR检测粉防己碱对外排泵基因表达的影响,分别敲除主要外排泵基因CDR1、CDR2和MDR1,研究这些基因对氟康唑耐受性的影响,并评估外排泵抑制剂维拉帕米对氟康唑耐受性的影响。结果粉防己碱能够消除白念珠菌对氟康唑的耐受性。单独使用粉防己碱对外排泵基因表达无显著影响,但与氟康唑联合使用会显著抑制外排泵基因CDR1的表达。在耐受性菌株中,敲除CDR1或添加外排泵抑制剂维拉帕米均能消除耐受性。结论粉防己碱通过抑制外排泵基因CDR1的表达,从而消除白念珠菌对氟康唑的耐受性。本研究为深入探究药物协同作用以对抗白念珠菌对氟康唑的耐受性提供了线索与参考。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 susceptibility of SC5314 to fluconazole in the presence of tetrandrine was evaluated using the disk diffusion assay.The impact of tetrandrine 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 eliminates the fluconazole tolerance of C.albicans by suppressing the expression of the efflux pump gene CDR1.This study provides important clues for further exploring drug synergies to combat fluconazole tolerance in C.albicans.

关 键 词：白念珠菌 氟康唑 耐受 粉防己碱 外排 

分 类 号：R379.4[医药卫生—病原生物学]