Experimental evolution to discover mechanisms of multidrug resistance and new treatment strategies to combat the novel ‘superbug’ Candida auris.

Antifungal resistance is emerging on a scale that has never been documented before. Invasive, multidrug-resistant fungal infections are posing an increasing threat to public health, further complicated by the availability of only three major antifungal drug classes. The antifungal resistance crisis is embodied by the novel ‘superbug’ C. auris. After its first identification in 2009, this opportunistic pathogen has emerged worldwide and shown resistance to an extent that has not been observed in other Candida species. Despite being the first fungus to be considered an urgent threat by the CDC, insights into the mechanisms underlying its multidrug resistance are still lacking. In the past, antifungal resistance has mainly been studied by performing whole-genome sequencing on clinical isolates. This however poses many challenges in terms of unavailability of the parental genotype and difficulties in identifying resistance related mutations. In this project we will eliminate these problems by performing experimental evolution both in vitro and in vivo. A completely new approach to studying antifungal resistance which will allow us to not only acquire multidrug resistant C. auris strains but also test new treatment strategies on their ability to impede resistance. Eventually this project will result in a thorough understanding of the molecular mechanisms that govern resistance and provide indications towards new treatment strategies that might lead to clinical recommendations.