Filamentation in <i>Candida auris</i>, an emerging fungal pathogen of humans: passage through the mammalian body induces a heritable phenotypic switch

<p>Morphological plasticity has historically been an indicator of increased virulence among fungal pathogens, allowing rapid adaptation to changing environments. <i>Candida auris</i> has been identified as an emerging multidrug-resistant human pathogen of global importance. Since the discovery of this species, it has been thought that <i>C. auris</i> is incapable of filamentous growth. Here, we report the discovery of filamentation and three distinct cell types in <i>C. auris</i>: typical yeast, filamentation-competent (FC) yeast, and filamentous cells. These cell types form a novel phenotypic switching system that contains a heritable (typical yeast-filament) and a nonheritable (FC-filament) switch. Intriguingly, the heritable switch between the typical yeast and the FC/filamentous phenotype is triggered by passage through a mammalian body, whereas the switch between the FC and filamentous phenotype is nonheritable and temperature-dependent. Low temperatures favor the filamentous phenotype, whereas high temperatures promote the FC yeast phenotype. Systemic in vivo and in vitro investigations were used to characterize phenotype-specific variations in global gene expression, secreted aspartyl proteinase (SAP) activity, and changes in virulence, indicating potential for niche-specific adaptations. Taken together, our study not only sheds light on the pathogenesis and biology of <i>C. auris</i> but also provides a novel example of morphological and epigenetic switching in fungi.</p>