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Updated: Jul 10, 2025

Whole Genome Sequencing of Candida glabrata for Detection of Markers of Antifungal Drug Resistance
Published on: December 28, 2017
The Microevolution of Antifungal Drug Resistance in Pathogenic Fungi
1School of Science, RMIT University, Melbourne, VIC 3085, Australia.
Abstract:
The mortality rates of invasive fungal infections remain high because of the limited number of antifungal drugs available and antifungal drug resistance, which can rapidly evolve during treatment. Mutations in key resistance genes such as ERG11 were postulated to be the predominant cause of antifungal drug resistance in the clinic. However, recent advances in whole genome sequencing have revealed that there are multiple mechanisms leading to the microevolution of resistance. In many fungal species, resistance can emerge through ERG11-independent mechanisms and through the accumulation of mutations in many genes to generate a polygenic resistance phenotype. In addition, genome sequencing has revealed that full or partial aneuploidy commonly occurs in clinical or microevolved in vitro isolates to confer antifungal resistance. This review will provide an overview of the mutations known to be selected during the adaptive microevolution of antifungal drug resistance and focus on how recent advances in genome sequencing technology have enhanced our understanding of this process.
Insights
Antifungal drug resistance in invasive fungal infections is a major challenge. Genome sequencing reveals resistance evolves through various genetic changes, not just single gene mutations, offering new insights for treatment.
Area of Science:
- Medical Mycology
- Genomics
- Antimicrobial Resistance
Background:
- Invasive fungal infections have high mortality rates due to limited antifungal drugs and evolving resistance.
- Antifungal drug resistance is a significant clinical challenge, necessitating a deeper understanding of its evolutionary mechanisms.
Purpose of the Study:
- To review mutations selected during the adaptive microevolution of antifungal drug resistance.
- To highlight how advances in genome sequencing have improved understanding of antifungal resistance evolution.
Main Methods:
- Review of existing literature on antifungal drug resistance.
- Analysis of findings from whole genome sequencing studies in fungal isolates.
- Examination of genetic mutations and aneuploidy associated with resistance.
Main Results:
- Antifungal resistance can emerge through ERG11-independent mechanisms.
- Polygenic resistance phenotypes arise from accumulated mutations in multiple genes.
- Aneuploidy (full or partial) is a common mechanism conferring antifungal resistance in clinical and in vitro isolates.
Conclusions:
- Antifungal resistance evolution is more complex than previously thought, involving multiple genetic pathways.
- Genome sequencing technologies are crucial for uncovering the diverse mechanisms of antifungal resistance.
- Understanding these microevolutionary processes is key to developing effective antifungal therapies.
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