Abstract
The basis for commitment to cell division in late G1 phase, called Start in yeast, is a critical but still poorly understood aspect of eukaryotic cell proliferation. Most dividing cells accumulate mass and grow to a critical cell size before traversing the cell cycle. This size threshold couples cell growth to division and thereby establishes long-term size homeostasis. At present, mechanisms involved in cell size homeostasis in fungal pathogens are not well described. Our previous survey of the size phenome inCandida albicans focused on 279 unique mutants enriched mainly in kinases and transcription factors (Sellam et al. PLoS Genet 15:e1008052, 2019). To uncover novel size regulators inC. albicans and highlight potential innovation within cell size control in pathogenic fungi, we expanded our genetic survey of cell size to include 1301 strains from the GRACE (Gene Replacement and Conditional Expression) collection. The current investigation uncovered both known and novel biological processes required for cell size homeostasis inC. albicans. We also confirmed the plasticity of the size control network as fewC. albicans size genes overlapped with those of the budding yeastSaccharomyces cerevisiae. Many new size genes ofC. albicans were associated with biological processes that were not previously linked to cell size control and offer an opportunity for future investigation. Additional work is needed to understand if mitochondrial activity is a critical element of the metric that dictates cell size inC. albicans and whether modulation of the onset of actomyosin ring constriction is an additional size checkpoint.
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Acknowledgements
We thank the National Research Council (NRC) Canada for providing the GRACE mutant collection.
Funding
This work was supported by grants from the Natural Sciences and Engineering Research Council of Canada (NSERC discovery grant) to AS. AS is supported by the Fonds de Recherche du Québec -Santé J2 salary award.
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Julien Chaillot
Present address: Centre de Recherche Paul Pascal, Unité Mixte de Recherche 5031, Université de Bordeaux, Centre National de la Recherche Scientifique, 33600, Pessac, France
Authors and Affiliations
Department of Microbiology, Infectious Diseases and Immunology, Faculty of Medicine, Université Laval, Quebec City, QC, Canada
Julien Chaillot
Department of Biochemistry and Biomedical Sciences, David Braley Center for Antibiotic Discovery, Michael G. DeGroote Institute for Infectious Disease Research, McMaster University, Hamilton, ON, Canada
Michael A. Cook
Montreal Heart Institute, Université de Montréal, Montréal, QC, Canada
Adnane Sellam
Department of Microbiology, Infectious Diseases and Immunology, Faculty of Medicine, Université de Montréal, Montréal, QC, Canada
Adnane Sellam
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All authors contributed to the study conception and design. JC and AS: performed the genetic size screen and wrote the manuscript draft. MAC: generated R scripts for data analysis. All authors read and approved the final manuscript.
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Correspondence toAdnane Sellam.
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294_2022_1260_MOESM1_ESM.xlsx
Supplementary file1 Excel spreadsheet containing experimental size data of individual mutant from theC. albicans GRACE collection. Mean, median and mode size of each strain are shown (XLSX 79 KB)
294_2022_1260_MOESM2_ESM.xlsx
Supplementary file2 Excel spreadsheet listingC. albicans size mutants. Mutants for whom median size was increased or decreased by 20% as compared to the parental WT strains are indicated (XLSX 19 KB)
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Chaillot, J., Cook, M.A. & Sellam, A. Novel determinants of cell size homeostasis in the opportunistic yeastCandida albicans.Curr Genet69, 67–75 (2023). https://doi.org/10.1007/s00294-022-01260-0
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