Cellular quiescence in Candida albicans

Microbial cells frequently enter a quiescent state, a reversible non-proliferative phase that enables survivalunder nutrient-limited and stressful conditions. Despite its physiological significance, the properties andimplications of quiescence in Candida albicans, an opportunistic fungal pathogen, remain largely unexplored. In this study, we characterize the morphological, metabolic, and genomic features of quiescent C. albicans cells and assess their implications for antifungal treatment efficacy. Using growth conditions we defined as rich and minimal, we establish that C. albicans undergoes distinct morphological changes upon entry into quiescence, including reduced cell size, increased density, and alterations in mitochondrial activity.Transcriptomic profiling reveals extensive metabolic reprogramming, with downregulation of ribosomalbiogenesis and upregulation of stress response pathways. Functional assays demonstrate that quiescent cells exhibit increased resistance to heat stress and antifungal treatment, underscoring the potential role ofquiescence in drug tolerance. Additionally, we show that quiescent cells can efficiently re-enter the cell cycleupon nutrient replenishment. Our findings highlight quiescence as a critical survival strategy in C. albicans, with potential implications for antifungal therapy efficacy and persistent infections. Understanding the molecular mechanisms underlying fungal quiescence may inform strategies to enhance treatment strategies and mitigate recurrent infections.