Transcriptomics and Phenotyping Define Genetic Signatures Associated with Echinocandin Resistance in Candida auris
Sabrina Jenull, Raju Shivarathri, Irina Tsymala, Philipp Penninger, Trinh Phan-Canh, Filomena Nogueira, Manju Chauhan, Ashutosh Singh, Andriy Petryshyn, Anton Stoiber, Anuradha Chowdhary, Neeraj Chauhan, Karl Kuchler
Abstract
The surge in antimicrobial drug resistance in some bacterial and fungal pathogens constitutes a significant challenge to health care facilities. The emerging human fungal pathogen Candida auris has been particularly concerning, as isolates can display pan-antifungal resistance traits against all drugs, including echinocandins. However, the mechanisms underlying this phenotypic diversity remain poorly understood. We identify transcriptomic signatures in C. auris isolates resistant to otherwise fungicidal echinocandins. We identify a set of differentially expressed genes shared by resistant strains compared to unrelated susceptible isolates. Moreover, phenotyping demonstrates that resistant strains show distinct behaviors, with implications for host-pathogen interactions. Hence, this work provides a solid basis to identify the mechanistic links between antifungal multidrug resistance and fitness costs that affect the interaction of C. auris with host immune defenses.