Related Experiment Video
Updated: Aug 7, 2026
Small-Scale Plasma Membrane Preparation for the Analysis of Candida albicans Cdr1-mGFPHis
Published on: June 13, 2021
Multiple cis-acting sequences mediate upregulation of the MDR1 efflux pump in a fluconazole-resistant clinical
Davina Hiller1, Stephanie Stahl, Joachim Morschhäuser
1Institut für Molekulare Infektionsbiologie, Universität Würzburg, Röntgenring 11, D-97070 Würzburg, Germany.
Abstract:
Overexpression of the MDR1 gene, which encodes a multidrug efflux pump of the major facilitator superfamily, is a frequent cause of resistance to the antimycotic agent fluconazole and other metabolic inhibitors in clinical Candida albicans strains. Constitutive MDR1 overexpression in such strains is caused by mutations in as yet unknown trans-regulatory factors. In order to identify the cis-acting sequences in the MDR1 regulatory region that mediate constitutive MDR1 upregulation, we performed a promoter deletion analysis in the genetic background of an MDR1-overexpressing clinical C. albicans isolate. We found that several different regions in the MDR1 promoter can mediate MDR1 overexpression in this isolate. In contrast, deletion of one of these regions abolished benomyl-induced MDR1 expression in a C. albicans laboratory strain. These results suggest that multiple transcription factors control expression of the MDR1 efflux pump in C. albicans and that the mutation(s) that causes constitutive MDR1 overexpression and drug resistance in clinical C. albicans isolates affects the activities of several of these transcription factors.
Insights
Mutations in Candida albicans cause overexpression of the MDR1 gene, leading to resistance against antifungal drugs like fluconazole. This study identifies specific promoter regions involved in this drug resistance mechanism.
Area of Science:
- Molecular Biology
- Mycology
- Antimicrobial Resistance
Background:
- The MDR1 gene in Candida albicans encodes a multidrug efflux pump, crucial for resistance to antifungals like fluconazole.
- Overexpression of MDR1 in clinical strains is a primary driver of antifungal drug resistance.
- Constitutive MDR1 overexpression is linked to mutations in unknown trans-regulatory factors.
Purpose of the Study:
- To identify cis-acting sequences within the MDR1 promoter responsible for constitutive MDR1 upregulation.
- To understand the regulatory mechanisms underlying MDR1 overexpression and drug resistance in Candida albicans.
Main Methods:
- Conducted a promoter deletion analysis of the MDR1 gene.
- Utilized an MDR1-overexpressing clinical Candida albicans isolate and a laboratory strain.
- Assessed the impact of promoter deletions on MDR1 expression, including benomyl-induced expression.
Main Results:
- Identified multiple distinct regions in the MDR1 promoter that can mediate MDR1 overexpression in a clinical isolate.
- Demonstrated that deletion of a specific promoter region abolished benomyl-induced MDR1 expression in a laboratory strain.
- Indicated that mutations causing constitutive overexpression affect the activity of multiple transcription factors.
Conclusions:
- Multiple transcription factors regulate the MDR1 efflux pump in Candida albicans.
- The genetic mutations responsible for constitutive MDR1 overexpression and drug resistance impact several transcription factors.
- Understanding these regulatory elements is key to overcoming antifungal resistance in clinical Candida albicans infections.
