Novel determinants of cell size homeostasis in the opportunistic yeast Candida albicans

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 in Candida 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 in C. 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 in C. albicans. We also confirmed the plasticity of the size control network as few C. albicans size genes overlapped with those of the budding yeast Saccharomyces cerevisiae. Many new size genes of C. 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 in C. albicans and whether modulation of the onset of actomyosin ring constriction is an additional size checkpoint.