Studies naar antimycotische resistentie en tolerantie bij Candida auris: Ontdekking en validatie van nieuwe mechanismen

Antifungal resistance is escalating at an alarming rate, posing a serious global health threat due to the limited availability of only three main antifungal drug classes. The emergence of Candidozyma auris (syn. Candida auris), a multidrug-resistant fungal pathogen, epitomizes this crisis. Since its first identification in 2009, C. auris has caused numerous hospital outbreaks worldwide and demonstrated levels of resistance unprecedented among fungi. Despite being classified by the CDC as an urgent public health threat, the molecular mechanisms driving its resistance remained poorly understood. This thesis addresses this critical gap by establishing reliable molecular and gene-editing tools to investigate how C. auris acquires and maintains antifungal resistance and tolerance. Through a combination of experimental evolution and molecular analysis, the project uncovered novel, potentially clinically relevant mechanisms of amphotericin B resistance, as well as the first evidence of genetically encoded echinocandin tolerance. Together, these findings provide crucial insights into the biology of C. auris and offer new perspectives for improving antifungal treatment strategies.