Defining the Candidozyma auris pan-genome and essentiality

Abstract

Candidozyma auris is a multi-drug resistant fungal pathogen that causes hospital outbreaks, but genetic variation and gene function in this organism remain undercharacterized. Here, we performed pangenome analysis on 695 genetically representative isolates of C. auris and found that only 2.6% of gene families varied in their presence, mainly consisting of gene loss events or clade-specific genes, highlighting the clonal nature of these strains. Using microbial genome-wide association, we identified two loci associated with altered keratinocyte adherence, including genes with unknown function. To look broadly at gene function, we developed a genome-scale insertional mutagenesis approach and identified 614 high-confidence essential genes. Nearly one-third of these genes exhibited divergent essentiality compared to the model yeasts Candida albicans and Saccharomyces cerevisiae. Together, this study highlights organism-specific biology and provides a comprehensive resource for identifying species-specific determinants of virulence and targets for antifungal drug development.