Convergent evolution on <i>RBA1</i> regulates <i>Candidozyma auris</i> host adaptation

<i>Candidozyma auris</i> is an emerging healthcare-associated fungal pathogen, increasingly isolated from clinical outbreaks, with a high propensity to colonize patients and the medical environment. Here, we leveraged <i>C. auris</i> isolates from multi-facility clinical outbreaks to identify genomic patho-adaptations promoting persistence and dissemination in the healthcare environment. Genomic and phylogenetic analyses revealed loss-of-function mutations in the uncharacterized <i>C. auris</i> transcription factor gene <i>RBA1</i> to have independently emerged multiple times within these outbreaks. We demonstrate loss of <i>RBA1</i> increases <i>C. auris</i> adhesion to plastic and human keratinocytes, enhances biofilm formation, and exacerbates fungal burden in a mouse model of catheter-associated urinary tract infection. Finally, we uncover mutations in <i>RBA1</i> have emerged during multiple <i>C. auris</i> outbreaks across the globe, and that <i>RBA1</i> mutant lineages are present among large ongoing clinical outbreaks. These results reveal loss-of-function mutations in <i>C. auris RBA1</i> as a novel and clinically relevant genetic determinant of enhanced outbreak characteristics.