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Expression of Major Efflux Pumps in Fluconazole-Resistant Candida albicans
Babak Pourakbari1, Mostafa Teymuri2, Shima Mahmoudi1
1Pediatric Infectious Disease Research Center, Tehran University of Medical Science, Tehran. Iran.
Introduction:
Resistance to azole antifungals is considered as a significant problem in Candida albicans infections. Several molecular mechanisms of fluconazole resistance including alterations in the gene encoding the target enzyme ERG11 or overexpression of efflux pump genes including CDR1, CDR2, MDR1, MDR2 and FLU1 have been reported. The aim of this study was to investigate overexpression of efflux pump genes including CDR1, CDR2, MDR1, MDR2 and FLU1 in fluconazole- resistant C. albicans.
Material And Methods:
In this study, a total of 97 clinical isolates of C. albicans were isolated from hospitalized children in Children medical center, an Iranian referral hospital. Fluconazole susceptibility testing of C. albicans was performed using the broth microdilution method according to the CLSI guideline. Expression of CDR1, CDR2, MDR1, MDR2 and FLU1 genes was measured using quantitative real-time reverse transcription-polymerase chain reaction (RT-PCR) and 18SrRNA gene was used as a housekeeping gene.
Results:
Among 97 C. albicans isolates, 5 strains were categorized as fluconazoleresistant. Overexpression of CDR1, CDR2 and MDR2 genes was found in all isolates. MDR1 overexpression was observed in four resistant isolates. None of the resistant strains displayed increases in FLU1 transcript levels.
Conclusion:
Overexpression of the CDR1, CDR2, MDR1 and MDR2 genes might play an important role in fluconazole-resistant C. albicans. No link between expression of FLU1 and fluconazole resistance was found.
Insights
Overexpression of efflux pump genes, including CDR1, CDR2, MDR1, and MDR2, is linked to fluconazole resistance in Candida albicans. The FLU1 gene showed no correlation with this resistance in clinical isolates.
Area of Science:
- Mycology
- Infectious Diseases
- Molecular Biology
Background:
- Azole antifungal resistance is a major challenge in treating Candida albicans infections.
- Mechanisms include target enzyme alterations (ERG11) and efflux pump gene overexpression (CDR1, CDR2, MDR1, MDR2, FLU1).
Purpose of the Study:
- To investigate the overexpression of efflux pump genes (CDR1, CDR2, MDR1, MDR2, FLU1) in fluconazole-resistant Candida albicans.
Main Methods:
- Studied 97 clinical Candida albicans isolates from a pediatric hospital.
- Assessed fluconazole susceptibility using broth microdilution (CLSI guidelines).
- Quantified gene expression (CDR1, CDR2, MDR1, MDR2, FLU1) via RT-PCR, using 18SrRNA as a reference.
Main Results:
- Five out of 97 isolates were fluconazole-resistant.
- All resistant isolates showed overexpression of CDR1, CDR2, and MDR2 genes.
- MDR1 was overexpressed in four resistant isolates; FLU1 showed no increased transcript levels.
Conclusions:
- Overexpression of CDR1, CDR2, MDR1, and MDR2 genes likely contributes significantly to fluconazole resistance in Candida albicans.
- No association was found between FLU1 gene expression and fluconazole resistance.
