AI Article Synopsis
- Tetrandrine (TET) can reverse fluconazole resistance in Candida albicans by affecting specific drug resistance genes and energy metabolism.
- The study measured expression levels of resistance genes and ATP levels in both fluconazole-sensitive and resistant strains treated with TET and fluconazole (FLC).
- Results showed that TET treatment altered expressions of resistance genes (CDR1, CDR2, MDR1, FLU1, ERG11) and reduced intracellular ATP in both sensitive and resistant strains, indicating a potential mechanism for overcoming drug resistance.
Article Abstract
Context: 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.
Materials And 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).
Discussion And Conclusion: 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.
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| http://dx.doi.org/10.3109/13880209.2013.764537 | DOI Listing |
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