Abstract
Candida auris is an emergent multidrug-resistant fungal pathogen causing increasing reports of outbreaks. While distantly related to C. albicans and C. glabrata, C. auris is closely related to rarely observed and often multidrug-resistant species from the C. haemulonii clade. Here, we analyze near complete genome assemblies for the four C. auris clades and three related species, and map intra- and inter-species rearrangements across the seven chromosomes. Using RNA-Seq-guided gene predictions, we find that most mating and meiosis genes are conserved and that clades contain either the MTLa or MTLα mating loci. Comparing the genomes of these emerging species to those of other Candida species identifies genes linked to drug resistance and virulence, including expanded families of transporters and lipases, as well as mutations and copy number variants in ERG11. Gene expression analysis identifies transporters and metabolic regulators specific to C. auris and those conserved with related species which may contribute to differences in drug response in this emerging fungal clade.
Highlights
Candida auris is an emergent multidrug-resistant fungal pathogen causing increasing reports of outbreaks
Despite the fact that C. auris is highly divergent from other Saccharomycetales yeasts from the CTG clade, which includes the common human pathogens C. albicans, Candida tropicalis, and Candida parapsilosis, most of our limited current knowledge of C. auris resistance and virulence had been inferred based on conservation of genes associated with drug resistance and virulence in C. albicans or in C. glabrata, which is part of the distantly related Nakaseomyces clade
Using RNA-Seq we examine the response of two isolates of C. auris to antifungal drugs and detect the upregulation of transporters and metabolic regulators that have been previously associated with drug resistance in C. albicans
Summary
Candida auris is an emergent multidrug-resistant fungal pathogen causing increasing reports of outbreaks. C. auris causes bloodstream and other invasive and superficial infections, similar to a group of rarely observed, phylogenetically related species including Candida haemulonii, Candida duobushaemulonii, and Candida pseudohaemulonii[4,5]. These species display MDR, most commonly to amphotericin B and reduced susceptibility to azoles and echinocandins[4,5]. Phylogenetic studies revealed that C. auris belongs to the C. haemulonii clade and is distantly related to the more common human pathogenic species including Candida albicans and Candida glabrata[4,5,12,13].
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