Candida auris uses nutrient sensing to modulate virulence and host immune responses.

The emergence of Candida auris as a pathogen required host adaptation and evasion of mammalian immunity, but the mechanisms are poorly understood. We discovered that C. auris uses nutrient sensing to tune its virulence traits and modulate immune activation in changing environments. In glucose-rich conditions (relevant to blood), C. auris suppresses its virulence traits and evades immune detection. Conversely, non-fermentable carbon sources prevalent in skin activate adhesion and filamentation, thereby triggering macrophage responses. Activation of adhesion by non-fermentable carbon sources is recapitulated across diverse C. auris strains, while filamentation is heterogeneous. In-depth phenotyping of multiple clinical strains revealed that C. auris generates phenotypic heterogeneity by titrating expression of key transcriptional regulators dependent on nutrient inputs and genetic background. This modulates its virulence potential and controls proportional immune responses. Therefore, metabolic flexibility enables C. auris to optimize a critical trade-off: expressing virulence traits while minimizing immune recognition to colonize host tissues.