Genomic Diversity across Candida auris Clinical Isolates Shapes Rapid Development of Antifungal Resistance <i>In Vitro</i> and <i>In Vivo</i>
Laura S. Burrack, Robert T. Todd, Natthapon Soisangwan, Nathan P. Wiederhold, Anna Selmecki
Abstract
Drug resistant Candida auris infections are recognized by the CDC as an urgent threat. Here, we obtained and characterized a set of clinical isolates of C. auris including multiple isolates from the same patient. To understand how drug resistance arises, we evolved these isolates and found that resistance to fluconazole, the most commonly prescribed antifungal, can occur rapidly and that there are multiple pathways to resistance. During our experiment, resistance was gained, but it was not lost, even in the absence of drug. We also found that some C. auris isolates have higher mutation rates than others and are primed to acquire antifungal resistance mutations. Furthermore, we found that multidrug resistance can evolve within a single patient. Overall, our results highlight the high stability and high rates of acquisition of antifungal resistance of C. auris that allow evolution of pan-resistant, transmissible isolates in the clinic.