Learning Molecular Mechanisms of Fungal Adaptation using one of the Most Extremotolerant Fungi Known, Aureobasidium pullulans

Unlike model yeasts that thrive under mesophilic conditions, polyextremotolerant fungi grow and adapt to extreme and unfavorable conditions. We hypothesize that the cellular responses that enable stress tolerance in polyextremotolerant fungi are distinct or regulated differently from those of model yeasts. Understanding how these organisms can thrive in a broad range of stressful environments in a warming planet could lead to the identification of distinct pathways that enable rapid adaptation and increased pathogenicity in human hosts. Our focus is on Aureobasidium pullulans, a genetically tractable polyextremotolerant fungus. We will test whether phenotypic heterogeneity, possibly modulated by epigenetic factors, enables subpopulations of cells to adapt to diverse environmental conditions. We will also examine if the unusually diverse range of cell wall and plasma membrane biosynthetic enzymes and intrinsically disordered proteins helps cells withstand multiple stresses. Furthermore, we will explore how selection for genetic and epigenetic adaptations can render A. pullulans more thermotolerant and resistant to antifungals. This work should have far-reaching implications beyond A. pullulans and may be a template with which to understand other pathogens on the WHO priority list, including A. fumigatus and C. neoformans.