Metabolic reconstruction of the human pathogen Candida auris: using a cross-species approach for drug target prediction

Candida auris is an emerging human pathogen, associated with antifungal drug resistance and hospital candidiasis outbreaks. In this work, we present iRV973, the first reconstructed Genome-scale metabolic model (GSMM) for C. auris. The model was manually curated and experimentally validated, being able to accurately predict the specific growth rate of C. auris and the utilization of several sole carbon and nitrogen sources. The model was compared to GSMMs available for other pathogenic Candida species and exploited as a platform for cross-species comparison, aiming the analysis of their metabolic features and the identification of potential new antifungal targets common to the most prevalent pathogenic Candida species. From a metabolic point of view, we were able to identify unique enzymes in C. auris in comparison with other Candida species, which may represent unique metabolic features. Additionally, 50 enzymes were identified as potential drug targets, given their essentiality in conditions mimicking human serum, common to all four different Candida models analysed. These enzymes represent interesting drug targets for antifungal therapy, including some known targets of antifungal agents used in clinical practice, but also new potential drug targets without any human homolog or drug association in Candida species. This study describes the first validated genome-scale metabolic model for Candida auris, an emerging human pathogen, which provides a promising platform for global elucidation of the metabolic potential of C. auris, with expected impact in guiding the identification of new drug targets to tackle human candidiasis.