Chen L M, Xu Y H, Zhou C L, Zhao J, Li C Y, Wang R
Department of Dermatology, Qilu Hospital of Shandong University, Jinan, China.
J Int Med Res. 2010 Mar-Apr;38(2):536-45. doi: 10.1177/147323001003800216.
This study was designed to investigate potential resistance mechanisms by studying the expression of resistant genes in 14 fluconazole-resistant Candida albicans isolates, with G487T and T916C mutations in the 14alpha-demethylase (ERG11) gene, collected from human immunodeficiency virus uninfected patients and a fluconazole-susceptible control strain. The in vitro susceptibilities of the C. albicans isolates to fluconazole were determined using the broth microdilution method and a disc diffusion assay. Expression of Candida drug resistance (CDR)1, CDR2, ERG11, fluconazole resistance (FLU)1 and multidrug resistance (MDR)1 genes was measured using real-time reverse transcription-polymerase chain reaction and evaluated relative to the expression of the control gene 18SrRNA. The CDR1 and CDR2 genes were upregulated in all the fluconazole-resistant C. albicans isolates, whereas only a few isolates showed high expression of MDR1, FLU1 and ERG11 genes compared with the control strain. In conclusion, overexpression of the CDR1 and CDR2 genes may play an important role in fluconazole-resistant C. albicans with G487T and T916C mutations.
本研究旨在通过研究14株氟康唑耐药白色念珠菌分离株中耐药基因的表达情况,来探究潜在的耐药机制。这些分离株来自未感染人类免疫缺陷病毒的患者,其14α-脱甲基酶(ERG11)基因存在G487T和T916C突变,并设置了一株氟康唑敏感对照菌株。采用肉汤微量稀释法和纸片扩散法测定白色念珠菌分离株对氟康唑的体外敏感性。使用实时逆转录-聚合酶链反应测定念珠菌耐药性(CDR)1、CDR2、ERG11、氟康唑耐药性(FLU)1和多药耐药性(MDR)1基因的表达,并相对于对照基因18SrRNA的表达进行评估。在所有氟康唑耐药的白色念珠菌分离株中,CDR1和CDR2基因均上调,而与对照菌株相比,只有少数分离株显示MDR1、FLU1和ERG11基因高表达。总之,CDR1和CDR2基因的过表达可能在具有G487T和T916C突变的氟康唑耐药白色念珠菌中起重要作用。