Replicative Aging Remodels the Cell Wall and Is Associated with Increased Intracellular Trafficking in Human Pathogenic Yeasts
Vanessa K. A. Silva, Somanon Bhattacharya, Natália Kronbauer Oliveira, Anne G. Savitt, Daniel Zamith‐Miranda, Joshua D. Nosanchuk, Bettina C. Fries
Abstract
Cryptococcus neoformans and Candida glabrata are two opportunistic human fungal pathogens that cause life-threatening diseases. During infection, both microorganisms have the ability to persist for long periods, and treatment failure can occur even if standard testing identifies the yeasts to be sensitive to antifungals. Replicative life span is a trait that is measured by the number of divisions a cell undergoes before death. Aging in fungi is associated with enhanced tolerance to antifungals and resistance to phagocytosis, and characterization of old cells may help identify novel antifungal targets. The cell wall remains an attractive target for new therapies because it is essential for fungi and is not present in humans. This study shows that the organization of the fungal cell wall changes remarkably during aging and becomes thicker and is associated with increased intracellular trafficking as well as the alteration of vacuole morphology and pH homeostasis.