Genomic Innovation and Virulence Evolution in the Emerging Human Fungal Pathogen Candida auris

Candida auris is an emerging human fungal pathogen and global public health threat. Composed of at least five highly clonal clades, major clinical management challenges have included nosocomial outbreaks, difficulties in identification and diagnosis, and increasing multiple drug resistance. With a crude mortality of 45% in invasive candidiasis, virulence is also accompanied by a highly adhesive, stress tolerant, and environmentally persistent phenotype. This review covers examples of the genomic innovation strategies that may drive evolution of virulence in C. auris. Chromosomal architecture varies between genetic clades, with evidence of major rearrangements, particularly in the less virulent clade II. As a normally haploid yeast, adaptive aneuploidy (and diploidy) has also been observed, including under drug stress, which may increase virulence. Several gene family expansions, including of hydrolase, adhesin, and transporter families, indicate diversified and polarised roles in virulence. Important genomic variation linked to differing virulence has even been identified within a single patient, including copy number variation and loss of function of the adhesin gene ALS4 in two otherwise highly related strains. We conclude our review by suggesting research topics that need greater attention including (1) moving fungal genomic enquiry closer to patients in clinical settings, (2) targeting ecological drivers of evolution and escalating environmental discovery as a priority, and (3) interdisciplinary investigation across microbiology and immunology to leverage comparative, molecular, and population genomics to understand and control invasive candidiasis caused by C. auris.