华西口腔医学杂志

• 专栏论著 • 上一篇    下一篇

药物流出泵基因在白假丝酵母菌生物膜耐药性产生机制中的作用

亓庆国1,2 Micheal. D. Lafleur2   

  1. 1.山东大学口腔医院口腔内科, 山东济南250012;2.Molecular Microbiology Laboratory, Department of Biology, Northeastern University, Boston MA 02115 USA
  • 收稿日期:2009-04-25 修回日期:2009-04-25 出版日期:2009-04-20 发布日期:2009-04-20
  • 通讯作者: 亓庆国,Tel:0531-88382213
  • 作者简介:亓庆国(1972-),男,山东人,副教授,博士
  • 基金资助:

    国家自然科学基金资助项目(30400498);中国博士后科学基金资助项目(20060390155)

Roles of drug efflux pump genes in the mechanism of Saccharomyces albicans biofilm drug tolerance

QI Qing-guo1,2, Micheal. D. Lafleur2   

  1. 1. Dept. of Oral Medicine, College of Stomatology,Shandong University,Jinan 250012, China; 2. Molecular Microbiology Laboratory, Department of Biology, Northeastern University, Boston MA 02115, USA
  • Received:2009-04-25 Revised:2009-04-25 Online:2009-04-20 Published:2009-04-20
  • Contact: QI Qing-guo,Tel:0531-88382213

摘要:

目的利用药物流出泵基因缺陷株,初步阐明药物流出泵基因CDR1、CDR2、MDR1在生物膜耐药性产生和表现型耐药菌株产生中的作用。方法以3种咪唑类抗真菌药物以及CDR1药物流出泵抑制剂作用于药物流出泵基因缺陷株形成的生物膜,采用XTT法和菌落计数的方法,分析药物流出泵基因在生物膜耐药性产生中的作用。结果药物流出泵基因对缺陷株形成的24 h生物膜SMIC80影响不大,生物膜表现型耐药株的产生与药物流出泵基因有关,抗真菌药物联合CDR1基因抑制剂在一定程度上能够帮助杀灭白假丝酵母菌生物膜耐药株。结论药物流出泵基因对24 h生物膜表现出来的耐药性影响不大,而对生物膜产生的耐药株有重要作用。

关键词: 白假丝酵母菌, 生物膜, 耐药株, 药物流出泵

Abstract:

Objective Saccharomyces albicans is the main opportunistic pathogen which is also the common member of oral microflora, and the biofilms they formed have spontaneous drug tolerance compared with planktonic ones. Saccharomyces biofilm population can produce subpopulation of cells which can tolerant high concentration of antifungal drugs. They are called persisters. Many researches indicated that drug efflux gene such as CDR or MDR gene plays the very important roles in yeast drug resistance. The objective of this study is to illuminate the mechanism of Saccharomyces albicans biofilm drug tolerance related with drug efflux gene, especially to the persisters formation. Methods Test the minimal inhibitory concentration(MIC) and SMIC80 ( sessile minimal inhibitory concentration 80%) of 24 h biofim of totally 7 defective strains of drug efflux pump gene with Amphotercin B. And treat the 24 h biofilm by fluconazole, micronazole, clotrimazole combined with CDR1 inhibitor Enniatin B respectively and antifungal drugs alone as control, then scrapped the biofilm, cultured on the YPD agar. By CFU counting, the numbers of biofilm persisters were determined. Results All the defective strains have the similar MIC and SMIC80 for 24 h biofilm with wide type strains. CDR1 inhibitor Enniatin B can help antifungal drugs especially micronazole and clotrimazole to eliminate the biofilm persisters. Conclusion Saccharomyces albicans drug efflux gene may minor associated with 24 h biofilm drug tolerance. Drug efflux gene CDR1 may play an role in persisiters related biofilm drug tolerance.

Key words: Saccharomyces albicans, biofilm, drug tolerance, drug efflux gene