Candida auris uses nutrient sensing to titrate its virulence potential and modulate immune response for host colonisation

Abstract 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 potential and control immune activation in changing environments. In glucose-rich conditions (relevant to blood), C. auris suppresses its virulence traits and evades immune detection. Conversely, carbon sources prevalent in skin activate adhesion and filamentation, thereby triggering robust macrophage responses. 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 dials-up or -down its virulence potential and controls proportional immune responses and host colonisation. Therefore, metabolic flexibility enables C. auris to optimise a critical trade-off: expressing traits for tissue colonization while minimizing immune recognition. This establishes how C. auris adjusts its virulence and immune evasion to thrive in host environments.