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Macrophage Cholesterol Depletion and Its Effect on the Phagocytosis of Cryptococcus neoformans
Published on: December 19, 2014
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Cellular and genetic changes during and after fluconazole exposure in Cryptococcus neoformans
Samah H Albehaijani1, Tien Huynh2, Kylie J Boyce2
1School of Science, RMIT University, Melbourne, Victoria, Australia; Department of Biology, College of Science, Qassim University, Buraydah, Saudi Arabia.
International Journal of Antimicrobial Agents
|April 19, 2025
Summary
The antifungal drug fluconazole causes widespread genome changes in Cryptococcus neoformans, leading to varied permanent alterations and potential drug resistance after treatment cessation.
Area of Science:
- Mycology
- Genetics
- Antimicrobial Resistance
Background:
- Genome replication validity is crucial for fungal survival, with errors leading to ploidy changes.
- Ploidy changes in Cryptococcus neoformans are observed in clinical settings, often linked to fluconazole exposure and chromosome 1 aneuploidy.
Purpose of the Study:
- To investigate the impact of fluconazole on transient aneuploidy in Cryptococcus neoformans.
- To identify genetic pathways involved in fluconazole-induced aneuploidy.
Main Methods:
- Examined 30 genes related to chromosome organization, DNA damage checkpoints, and stress signaling.
- Investigated ploidy status (haploid, diploid, polyploid) and species to find commonalities for drug treatment.
Main Results:
- Fluconazole increased DNA content, cell size, and chromosomal changes in wildtype and mutant strains.
- Permanent, variable changes occurred after fluconazole removal.
- Mutants like tel1∆, mrc1∆, and hog1∆ showed a lack of chromosomal changes, indicating their role in aneuploidy.
Conclusions:
- Fluconazole affects the entire genome, not just specific chromosomes, leading to heterogeneous permanent changes post-treatment.
- This genomic heterogeneity may contribute to long-term consequences, including antifungal drug resistance.
