Quantification of CDR1 Gene Expression in Fluconazole Resistant Candida Glabrata Strains Using Real-time PCR

Shadi Shahrokhi1, Fatemeh Noorbakhsh1, Sassan Rezaie2

  • 1Dept. of Microbiology, Islamic Azad University, Varamin-Pishva Branch, Varamin, Iran.

Abstract

Insights

Fluconazole resistance in Candida glabrata is linked to increased CDR1 gene expression. This study highlights the role of CDR1 in antifungal resistance, suggesting it as a target for further investigation.

Area of Science:

  • Medical Mycology
  • Molecular Biology
  • Antimicrobial Resistance

Background:

  • Candida glabrata is a significant cause of life-threatening fungal infections.
  • Increasing fluconazole resistance in C. glabrata is a growing clinical concern.
  • Overexpression or mutations in ATP-binding cassette (ABC) transporter genes, like CgCDR1 and CgCDR2, contribute to fluconazole resistance.

Purpose of the Study:

  • To evaluate the CDR1 gene expression level as a key mechanism in fluconazole resistance of C. glabrata.

Main Methods:

  • Clinical isolates of C. glabrata were collected and validated.
  • Antifungal susceptibility testing to fluconazole was performed using CLSI protocols.
  • Real-time PCR was used to measure CDR1 mRNA expression levels in selected isolates.

Main Results:

  • 32% of strains were susceptible, 64% showed dose-dependent (DD) resistance, and 4% were resistant to fluconazole.
  • Resistant C. glabrata strains (MIC≥64 μg/ml) exhibited significant overexpression of the CDR1 gene compared to susceptible strains.
  • Real-time PCR analysis confirmed the correlation between CDR1 overexpression and fluconazole resistance.

Conclusions:

  • The CgCDR1 gene plays a crucial role in fluconazole resistance in Candida glabrata.
  • Investigating the transporter functions of CgCDR1 is necessary for understanding and combating antifungal resistance.
  • Findings emphasize the importance of monitoring gene expression in clinical isolates to guide treatment strategies.