Aneuploidy confers a unique transcriptional and phenotypic profile to Candida albicans

Abstract Inaccurate chromosome segregation can lead to the formation of aneuploid cells that harbor an imbalanced complement of chromosomes. Several fungal species are not only able to tolerate the detrimental effects of aneuploidy but can use it to adapt to environmental pressures. The fungal patho...

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Main Authors: Anna I. Mackey, Robert J. Fillinger, P. Shane Hendricks, Gregory J. Thomson, Christina A. Cuomo, Richard J. Bennett, Matthew Z. Anderson
Format: Article
Language:English
Published: Nature Portfolio 2025-04-01
Series:Nature Communications
Online Access:https://doi.org/10.1038/s41467-025-58457-3
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author Anna I. Mackey
Robert J. Fillinger
P. Shane Hendricks
Gregory J. Thomson
Christina A. Cuomo
Richard J. Bennett
Matthew Z. Anderson
author_facet Anna I. Mackey
Robert J. Fillinger
P. Shane Hendricks
Gregory J. Thomson
Christina A. Cuomo
Richard J. Bennett
Matthew Z. Anderson
author_sort Anna I. Mackey
collection DOAJ
description Abstract Inaccurate chromosome segregation can lead to the formation of aneuploid cells that harbor an imbalanced complement of chromosomes. Several fungal species are not only able to tolerate the detrimental effects of aneuploidy but can use it to adapt to environmental pressures. The fungal pathobiont Candida albicans frequently acquires supernumerary chromosomes that enable growth in the presence of antifungal drugs or in specific host niches, yet the transcriptional changes associated with aneuploidy are not globally defined. Here, a karyotypically diverse set of C. albicans strains revealed that expression generally correlated with gene copy number regardless of the strain karyotype. Unexpectedly, aneuploid strains shared a characteristic transcriptional profile that was distinct from a generalized environmental stress response previously defined in aneuploid yeast cells. This aneuploid transcriptional response led to altered growth and oxidative balances relative to euploid control strains. The increased expression of reactive oxygen species (ROS) mitigating enzymes in aneuploid cells reduced the levels of ROS but caused an acute sensitivity to both internal and external sources of oxidative stress. Taken together, our work demonstrates common transcriptional and phenotypic features of aneuploid C. albicans cells with consequences for infection of different host niches and susceptibility to environmental stimuli.
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spelling doaj-art-7b9dcdc912064d98956fa324d23044192025-08-20T02:12:07ZengNature PortfolioNature Communications2041-17232025-04-0116111310.1038/s41467-025-58457-3Aneuploidy confers a unique transcriptional and phenotypic profile to Candida albicansAnna I. Mackey0Robert J. Fillinger1P. Shane Hendricks2Gregory J. Thomson3Christina A. Cuomo4Richard J. Bennett5Matthew Z. Anderson6Department of Microbiology, The Ohio State UniversityBiomedical Sciences Graduate Program, The Ohio State UniversityDepartment of Microbiology, The Ohio State UniversityDepartment of Molecular Microbiology and Immunology, Brown UniversityDepartment of Molecular Microbiology and Immunology, Brown UniversityDepartment of Molecular Microbiology and Immunology, Brown UniversityDepartment of Microbiology, The Ohio State UniversityAbstract Inaccurate chromosome segregation can lead to the formation of aneuploid cells that harbor an imbalanced complement of chromosomes. Several fungal species are not only able to tolerate the detrimental effects of aneuploidy but can use it to adapt to environmental pressures. The fungal pathobiont Candida albicans frequently acquires supernumerary chromosomes that enable growth in the presence of antifungal drugs or in specific host niches, yet the transcriptional changes associated with aneuploidy are not globally defined. Here, a karyotypically diverse set of C. albicans strains revealed that expression generally correlated with gene copy number regardless of the strain karyotype. Unexpectedly, aneuploid strains shared a characteristic transcriptional profile that was distinct from a generalized environmental stress response previously defined in aneuploid yeast cells. This aneuploid transcriptional response led to altered growth and oxidative balances relative to euploid control strains. The increased expression of reactive oxygen species (ROS) mitigating enzymes in aneuploid cells reduced the levels of ROS but caused an acute sensitivity to both internal and external sources of oxidative stress. Taken together, our work demonstrates common transcriptional and phenotypic features of aneuploid C. albicans cells with consequences for infection of different host niches and susceptibility to environmental stimuli.https://doi.org/10.1038/s41467-025-58457-3
spellingShingle Anna I. Mackey
Robert J. Fillinger
P. Shane Hendricks
Gregory J. Thomson
Christina A. Cuomo
Richard J. Bennett
Matthew Z. Anderson
Aneuploidy confers a unique transcriptional and phenotypic profile to Candida albicans
Nature Communications
title Aneuploidy confers a unique transcriptional and phenotypic profile to Candida albicans
title_full Aneuploidy confers a unique transcriptional and phenotypic profile to Candida albicans
title_fullStr Aneuploidy confers a unique transcriptional and phenotypic profile to Candida albicans
title_full_unstemmed Aneuploidy confers a unique transcriptional and phenotypic profile to Candida albicans
title_short Aneuploidy confers a unique transcriptional and phenotypic profile to Candida albicans
title_sort aneuploidy confers a unique transcriptional and phenotypic profile to candida albicans
url https://doi.org/10.1038/s41467-025-58457-3
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