上海交通大学学报（医学版）

上海交通大学学报（医学版）

• 论著（基础研究） • 上一篇    下一篇

光滑假丝酵母菌氟康唑耐药机制研究

姚冬婷，应春妹   

  1. 上海交通大学 医学院附属仁济医院检验科， 上海 200127
  • 出版日期:2014-01-28 发布日期:2014-01-29
  • 通讯作者: 应春妹, 电子信箱: ycmzh2012@163.com。
  • 作者简介:姚冬婷（1989—）， 女， 硕士生; 电子信箱: yaodongting@126.com。

Mechanisms of fluconazole resistance in clinical isolates of Candida glabrata

YAO Dong-ting, YING Chun-mei   

  1. Clinical Laboratory, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 201112, China
  • Online:2014-01-28 Published:2014-01-29

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摘要：

目的 探讨光滑假丝酵母菌CDR1、CDR2、SNQ2和ERG11基因mRNA表达差异以及ERG11基因突变在氟康唑耐药形成中的作用。方法 采用罗丹明6G试验比较氟康唑耐药组与敏感组的外排泵作用，Real-Time PCR检测外排相关基因CDR1、CDR2、SNQ2和ERG11表达情况。同时，对ERG11基因进行PCR扩增和测序，比较耐药组和敏感组的突变位点。结果 耐药组光滑假丝酵母菌外排泵功能明显强于敏感组，差异有统计学意义（P<0.01）。耐药组的CDR1和CDR2 mRNA表达水平显著高于敏感组（P<0.01，P<0.05）；但两组间SNQ2和ERG11 mRNA表达水平比较差异无统计学意义（P>0.05）。检测到ERG11基因4个突变位点，均为同义突变，其中3个突变位点在耐药组和敏感组中均出现，1个突变位点只在敏感组中出现。结论 外排泵功能在光滑假丝酵母菌氟康唑耐药过程中起重要作用。ERG11基因序列存在多态性，但未发现与氟康唑耐药相关的突变位点。

关键词: 光滑假丝酵母菌, 外排泵, ERG11, 氟康唑

Abstract:

Objective To investigate the different expression levels of CDR1, CDR2, SNQ2, and ERG11 genes and the mutation of ERG11 gene in order to explore their roles in inducing fluconazole resistance in Candida glabrata. Methods Efflux of rhodamine 6G was performed to evaluate the effects of efflux pumps. The expression levels of CDR1, CDR2, SNQ2, and ERG11 genes were determined by real-time PCR. Meanwhile, the sequences of ERG11 were determined by PCR based DNA sequencing. Mutation of ERG11 gene was compared between fluconazole resistant and susceptible isolates. Results Efflux pumps of fluconazole resistant isolates had stronger effects than fluconazole susceptible isolates, consistently with significant upregulation of CDR1 and CDR2 (P<0.01, P<0.05). But no remarkable difference was found in SNQ2 and ERG11 expression levels (P＞0.05). Four kinds of synonymous point mutation in ERG11 gene were found, which were three in both fluconazole resistant and susceptible isolates and one in susceptible isolates. Conclusion The efflux pumps play an important role in the development of fluconazole resistance in Candida glabrata. ERG11 gene mutation was found without association with the fluconazole resistance.

Key words: Candida glabrata, efflux pumps, ERG11, fluconazole