Chromosome 1 trisomy confers resistance to aureobasidin A in Candida albicans
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Updated: Aug 4, 2025
Small-Scale Plasma Membrane Preparation for the Analysis of Candida albicans Cdr1-mGFPHis
Published on: June 13, 2021
Lijun Zheng1, Yi Xu2, Yubo Dong2
1Department of Ultrasound Medicine, The Second Affiliated Hospital of Soochow University, Suzhou, China.
Introduction:
Candida albicans is a prevalent opportunistic human fungal pathogen. However, there are currently very few antifungal treatments available. Inositol phosphoryl ceramide synthase is an essential and fungal-specific protein that also provides a novel and promising antifungal target. Aureobasidin A is a widely used inhibitor of inositol phosphoryl ceramide synthase, however the mechanism of resistance to aureobasidin A is largely unknown in pathogenic fungi.
Methods:
Here we investigated how C. albicans adapted to low and high concentrations of aureobasidin A.
Results And Discussions:
We identified trisomy of chromosome 1 as the predominant mechanism of rapid adaptation. Resistance to aureobasidin A was unstable because of the inherent instability of aneuploids. Importantly, chromosome 1 trisomy simultaneously regulated genes which were associated with aureobasidin A resistance that are on this aneuploid chromosome as well as on other chromosomes. Furthermore, the pleiotropic effect of aneuploidy caused altered resistance not only to aureobasidin A but also to other antifungal drugs including caspofungin and 5-flucytosine. We posit aneuploidy provides a rapid and reversible mechanism of development of drug resistance and cross resistance in C. albicans.
Insights
Candida albicans rapidly adapts to aureobasidin A via chromosome 1 trisomy. This aneuploidy confers unstable, reversible drug resistance and cross-resistance to multiple antifungals.
Area of Science:
- Mycology
- Medical Mycology
- Antimicrobial Resistance
Background:
- Candida albicans is a major opportunistic fungal pathogen with limited treatment options.
- Inositol phosphoryl ceramide synthase is a validated antifungal target.
- Mechanisms of resistance to aureobasidin A, an inhibitor of this enzyme, are poorly understood.
Purpose of the Study:
- To investigate adaptation mechanisms of C. albicans to aureobasidin A.
- To understand the genetic basis of antifungal drug resistance.
Main Methods:
- Exposure of C. albicans to varying concentrations of aureobasidin A.
- Genomic analysis to identify adaptive mechanisms.
- Assessment of drug resistance profiles.
Main Results:
- Trisomy of chromosome 1 was identified as the primary mechanism for rapid adaptation.
- Aneuploidy conferred unstable, yet reversible, resistance to aureobasidin A.
- Chromosome 1 trisomy regulated genes on multiple chromosomes, leading to pleiotropic effects.
- Aneuploidy resulted in cross-resistance to caspofungin and 5-flucytosine.
Conclusions:
- Aneuploidy, specifically chromosome 1 trisomy, is a key mechanism for rapid antifungal drug resistance development in C. albicans.
- This mechanism provides a reversible and adaptable strategy for fungal survival.
- Aneuploidy contributes to cross-resistance, complicating treatment strategies.
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