Are Phenotypic Variability and Drug Resistance in the Emerging Fungal Pathogen Candida auris Generated by Genetic Recombination? (360G-Wellcome-212524_Z_18_Z)

I aim to elucidate how genetic diversity is achieved in the emerging multi-resistant fungal pathogen Candida auris and how this influences its drug resistance phenotype. Using genetic, genomic, and imaging approaches this project will determine why the strains of this fungus causing different outbreaks are highly variable, and how this diversity underpins its multi-drug resistance and other phenotypic characteristics. This project is based on hypotheses framed by pilot data that suggest that this fungus is sexually recombining with non-human host strains to generate novel pathogenic phenotypes. In Objective 1 I will determine whether (para)sexual reproduction generates genetic diversity in C. auris thus driving its evolution and dissemination. In Objective 2 I will establish how chromosomal variability maps onto the global population structure of this yeast and how this correlates with its drug resistance profile. In Objective 3 I will establish which genetic factors underlie the multi-drug resistance of clinical C. auris isolates. This project will provide crucially important mechanistic insight into the genetics of an emerging and dangerous human pathogen, C. auris; and has major implications for our understanding of its epidemiology, and significant potential to elucidate the origin of differences in drug resistance between clinical isolates of C. auris.