Related Experiment Video
Updated: Aug 24, 2026
Small-Scale Plasma Membrane Preparation for the Analysis of Candida albicans Cdr1-mGFPHis
Published on: June 13, 2021
A proteomic approach to understanding the development of multidrug-resistant Candida albicans strains
H Kusch1, K Biswas, S Schwanfelder
1Institut für Molekulare Infektionsbiologie, Julius-Maximilians-Universität Würzburg, Röntgenring 11, 97070, Würzburg, Germany.
Abstract:
Resistance of the pathogenic yeast Candida albicans to the antifungal agent fluconazole is often caused by the overexpression of genes that encode multidrug efflux pumps ( CDR1, CDR2, or MDR1). We have undertaken a proteomic approach to gain further insight into the regulatory network controlling efflux pump expression and drug resistance in C. albicans. Three pairs of matched fluconazole-susceptible and resistant clinical C. albicans isolates, in which drug resistance correlated with stable activation of MDR1 or CDR1/2, were analyzed for differences in their protein expression profiles. In two independent, MDR1-overexpressing, strains, additional up-regulated proteins were identified, which are encoded by the YPR127 gene and several members of the IFD ( YPL088) gene family. All are putative aldo-keto reductases of unknown function. These proteins were not up-regulated in a fluconazole-resistant strain that overexpressed CDR1 and CDR2 but not MDR1, indicating that expression of the various efflux pumps of C. albicans is controlled by different regulatory networks. To investigate the possible role of YPR127 in the resistance phenotype of the clinical isolates, we constitutively overexpressed the gene in a C. albicans laboratory strain. In addition, the gene was deleted in a C. albicans laboratory strain and in one of the drug-resistant clinical isolates in which it was overexpressed. Neither forced overexpression nor deletion of YPR127 affected the susceptibility of the strains to drugs and other toxic substances, suggesting that the regulatory networks which control the expression of efflux pumps in C. albicans also control genes involved in cellular functions not related to drug resistance.
Insights
This study investigated the protein expression changes in Candida albicans resistant to fluconazole. Researchers found that different efflux pump genes are regulated by distinct networks, and YPR127
Area of Science:
- Molecular Biology
- Mycology
- Proteomics
Background:
- Fluconazole resistance in Candida albicans is frequently linked to the overexpression of multidrug efflux pumps, including CDR1, CDR2, and MDR1.
- Understanding the regulatory mechanisms governing these efflux pumps is crucial for developing strategies to combat antifungal drug resistance.
Purpose of the Study:
- To elucidate the regulatory network controlling efflux pump expression and drug resistance in Candida albicans using a proteomic approach.
- To investigate the role of specific up-regulated genes, such as YPR127 and IFD family members, in fluconazole resistance.
Main Methods:
- Comparative proteomic analysis of matched fluconazole-susceptible and resistant clinical isolates of Candida albicans.
- Identification of differentially expressed proteins using mass spectrometry.
- Functional characterization of the YPR127 gene through overexpression and deletion in laboratory and clinical strains.
Main Results:
- Proteomic analysis revealed distinct protein expression profiles correlating with the overexpression of specific efflux pump genes (MDR1 vs. CDR1/2).
- YPR127 and IFD family genes were found to be up-regulated in MDR1-overexpressing strains but not in CDR1/2-overexpressing strains.
- Neither constitutive overexpression nor deletion of YPR127 significantly altered the drug susceptibility of Candida albicans strains.
Conclusions:
- The expression of different multidrug efflux pumps in Candida albicans is controlled by separate regulatory networks.
- The YPR127 gene and related aldo-keto reductases are likely involved in cellular functions unrelated to direct drug resistance mediated by efflux pumps.
- These findings suggest a complex regulatory landscape for drug resistance mechanisms in Candida albicans.
