Expression of Major Efflux Pumps in Fluconazole-Resistant Candida albicans

Abstract

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.

Keywords: C. albicans; FLU1; Fluconazole resistance; antifunds.; enzyme; real-Time PCR.