药物流出泵抑制剂联合咪康唑清除白假丝酵母菌生物被膜的研究

The research about Candida albicans biofilms eliminated by miconazole combined with drug efnux pump inhibitors

目的观察咪康唑分别与两种药物流出泵抑制剂联用清除耐药株（persister）的效果。方法白假丝酵母菌参考株YEM30，在96孔板中形成生物被膜（biofilm），CDR1抑制剂Enniatin B、CDR1／CDR2抑制剂Milbemycins α25单独或联合与咪康唑作用后，采用菌落形成单位（CFU）计数的方法统计耐药株的数量。采用SAS8．0统计软件包对数据进行q检验。结果咪康唑分别联合两种药物流出泵抑制剂清除生物被膜耐药株的效果明显优于咪康唑单独使用（P〈0．001），其中咪康唑与Enniatin B联用效果更佳。结论咪康唑与药物流出泵抑制剂联合应用具有清除生物被膜中表现型耐药株的作用，这为提高抗真菌治疗的效果提供了一条新途径和新思路。

Objective To investigate the effect of killing the biofilm persisters by miconazole combined with two compound which can inhibit the drug efflux of C. albicans. Methods Lab reference strains of C. albicans YEM30（ CAF2-1 ） formed the mature biofilm in the 96 well plates, and then treated with miconazole combined with Enniatin B （CDR1 inhibitor） and Milbemycins α25 （CDR1/CDR2 inhibitor） respectively. After incubated for 48 hours by CFU counting on the YPD plates, the analysis of persisters with SAS8.0 software package for q test. Results Miconazole combined with drug efflux inhibitor can kill more persisters than miconazole alone（ P 〈 0.001 ）, and combining with Enniatin B have a better results in eliminating the biofilm persisters than with Milbemycins α25. Conclusion Antifungal drugs combined with drug efflux pump inhibitors can kill more strains which can tolerate very high concentration of antifungal drugs. And searching the potential drug efflux pump inhibitors may be a new way for eliminating the persisters in biofilm, and consequently controlling the chronic recurrent fangal infectious diseases.