Overexpression of CDR1 and CDR2 genes plays an important role in fluconazole resistance in Candida albicans with G487T and T916C mutations

J Int Med Res. 2010 Mar-Apr;38(2):536-45. doi: 10.1177/147323001003800216.

Abstract

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.

MeSH terms

  • Antifungal Agents / pharmacology
  • Autoantigens / genetics*
  • Autoantigens / metabolism
  • Candida albicans / drug effects*
  • Candida albicans / genetics*
  • Candida albicans / isolation & purification
  • Candidiasis / genetics
  • Candidiasis / microbiology
  • Drug Resistance, Fungal / genetics*
  • Female
  • Fluconazole / pharmacology*
  • HIV Infections / genetics
  • HIV Infections / microbiology
  • HIV-1 / drug effects
  • Humans
  • Microbial Sensitivity Tests
  • Mutation / genetics*
  • Nerve Tissue Proteins / genetics*
  • Nerve Tissue Proteins / metabolism

Substances

  • Antifungal Agents
  • Autoantigens
  • CDR1 protein, human
  • CDR2 protein, human
  • Nerve Tissue Proteins
  • Fluconazole