title: Molecular mechanisms underlying the tetrandrine-mediated reversal of the fluconazole resistance of Candida albicans.
abstract: BACKGROUND
  Our previous study demonstrated that tetrandrine (TET) could reverse the resistance of Candida albicans to fluconazole.
  
  
  OBJECTIVE
  The aim of this study was to investigate the molecular mechanism underlying this action.
  
  
  METHODS
  Real-time reverse transcription polymerase chain reaction (real-time RT-PCR) was performed to compare the expression levels of the drug resistance genes CDR1, CDR2, MDR1, FLU1 and ERG11 in fluconazole-sensitive CA-3 and resistant CA-16 cells that were either treated with FLC and/or TET or left as untreated controls. In addition, intracellular ATP levels were measured using an ATP assay kit, and the expression level of the energy metabolism gene ADH1 was measured by real-time RT-PCR.
  
  
  RESULTS
  Compared with FLC/TET-free conditions, FLC + TET treatment strains showed statistically different (p < 0.05) expression of CDR1 and CDR2 (increased in the FLC-sensitive strains, while decreased in the FLC-resistant strains), MDR1 (increased in the FLC-resistant strains), FLU1 and ERG11 (increased in the FLC-sensitive strains), ADH1 (decreased in both the FLC-sensitive and the FLC-resistant strains). And also, the FLC + TET treatment decreased the intracellular ATP levels in both the FLC-sensitive and the FLC-resistant strains (p < 0.05).
  
  
  CONCLUSIONS
  These results suggest that changes in the expression levels of the drug resistance genes CDR1 and CDR2, the cellular ATP supply and the expression level of the energy metabolism gene ADH1 contribute to the TET-mediated reversal of the fluconazole resistance of C. albicans.
authors.affiliation: The First Affiliated Hospital and Institute of Mycology of Jinan University, Guangzhou, Guangdong, China.
authors.forename: Xiaoli
authors.initials: X
authors.lastname: Zhang
authors.forename: Hui
authors.initials: H
authors.lastname: Guo
authors.forename: Laiqiang
authors.initials: L
authors.lastname: Gao
authors.forename: Yanjun
authors.initials: Y
authors.lastname: Song
authors.forename: Shuixiu
authors.initials: S
authors.lastname: Li
authors.forename: Hong
authors.initials: H
authors.lastname: Zhang
mesh_terms: D018528:ATP-Binding Cassette Transporters / Q000235:genetics; D000255:Adenosine Triphosphate / Q000378:metabolism; D000426:Alcohol Dehydrogenase / Q000235:genetics; D000935:Antifungal Agents / Q000494:pharmacology*; D044182:Benzylisoquinolines / Q000494:pharmacology*; D002176:Candida albicans / Q000187:drug effects*; D025141:Drug Resistance, Fungal / Q000187:drug effects; D015725:Fluconazole / Q000494:pharmacology*; D005656:Fungal Proteins / Q000235:genetics; D005786:Gene Expression Regulation / Q000187:drug effects; D026901:Membrane Transport Proteins / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D018528:ATP-Binding Cassette Transporters; D000935:Antifungal Agents; D044182:Benzylisoquinolines; C094693:CDR1 protein, Candida albicans; D005656:Fungal Proteins; D026901:Membrane Transport Proteins; C009438:tetrandrine; D000255:Adenosine Triphosphate; D015725:Fluconazole; D000426:Alcohol Dehydrogenase