ABC转运蛋白与临床白念珠菌耐药  

ATP-binding-cassette transporters and fluconazole-resistance of clinical Candida albicans strains

作　　者：孙伟玮[1] 高平挥[1] 王英[2] 姜远英[1] 

机构地区：[1]第二军医大学药学院药理学教研室,上海200433 [2]第二军医大学长海医院皮肤科,上海200433

出　　处：《第二军医大学学报》2008年第9期1038-1041,共4页Academic Journal of Second Military Medical University

基　　金：国家重点基础研究发展计划(“973计划”,2005CB523105)~~

摘　　要：目的:研究临床氟康唑耐药白念珠菌中CDR1和CDR2基因的表达情况与耐药性产生的关系,探寻临床白念珠菌耐药的分子机制。方法:微量液基稀释法测定氟康唑对白念珠菌临床分离株的最低抑菌浓度(minimal inhibitory concentration,MIC);实时定量PCR(RQ-PCR)方法检测主动外排泵基因CDR1和CDR2的表达水平;用罗丹明6G(Rhodamine 6G)外转运实验检测罗丹明6G在CDR1、CDR2高表达的白念珠菌中的外排情况。结果:氟康唑耐药组菌株CDR1和CDR2高表达发生率显著高于敏感组菌株;而在加入葡萄糖提供能量后,CDR1和CDR2蛋白发生高表达的耐药菌株罗丹明6G外排能力显著增加。部分耐药菌株中未见CDR1和CDR2的高表达。结论:白念珠菌临床分离株对氟康唑的耐药性与ABC转运蛋白过度表达相关;ABC转运蛋白的高表达可以使药物外排能力增加,从而导致耐药性产生。同时可能有其他机制参与临床白念珠菌耐药性的生成。Objective：To explore the relationship between CDR1 and CDR2 expression and fluconazole-resistance in clinical Candida albicans strains, so as to explore the mechanism of drug-resistance in Candida albicans. Methods： The minimal inhibitory concentrations （MICs） of clinical Candida albicans strains to fluconazole were determined by broth microdilution method. The total RNA of fluconazole susceptible and fluconazole-resistant Candida albicans strains were extracted, and the expression of the CDR1 and CDR2 genes was examined by real-time RT-PCR. The efflux of Rhodamine 6G was determined in the strains highly expressing CDR1 and CDR2 genes. Results： The incidences of CDR1 and （or） CDR2 overexpression in fluconazole resistant strains were significantly higher than those in the fluconazole-sensitive stains. The efflux of Rhodamine 6G was significantly increased in the fluconazole-resistant strains when glucose was added, and overexpression of CDR1 and CDR2 were observed in theses strains. Some resistant strains showed no overexpression of CDR1 and CDR2. Conclusion： Fluconazole resistance in clinical Candida albicans strains is related to the overexpression of ABC transporter proteins. Overexpression of ABC transporters can increase the efflux of drugs and therefore lead to drug-resistance. Other mechanisms may also participate in the development of drug resistance in the clinical Candida albicans strains.

关 键 词：白念珠菌 氟康唑 真菌耐药性 ABC转运蛋白 罗丹明6G 

分 类 号：R379.4[医药卫生—病原生物学]