Munoz, J;
Gade, L;
Chow, N;
Loparev, V;
Juieng, P;
Farrer, R;
Litvintseva, A;
(2018)
Genomic basis of multidrug-resistance, mating, and virulence in Candida auris and related emerging species.
BioRxiv
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Abstract
Candida auris is an emergent fungal pathogen of rising health concern due to increasing reports of outbreaks in healthcare settings and resistance to multiple classes of antifungal drugs. While distantly related to the more common pathogens C. albicans and C. glabrata, C. auris is closely related to three rarely observed and often multidrug-resistant species, C. haemulonii, C. duobushaemulonii and C. pseudohaemulonii. Here, we generated and analyzed near complete genome assemblies and RNA-Seq-guided gene predictions for each of the four major C. auris clades and for C. haemulonii, C. duobushaemulonii and C. pseudohaemulonii. Our analyses mapped seven chromosomes and revealed chromosomal rearrangements between C. auris clades and related species. We found conservation of genes involved in mating and meiosis and identified both MTLa and MTLα C. auris isolates, strongly suggesting the potential for mating between clades. Gene conservation analysis highlighted that many genes linked to drug resistance and virulence in other pathogenic Candida species are conserved in C. auris and related species including expanded families of transporters and lipases, as well as mutations and copy number variants in ERG11 that confer drug resistance. In addition, we found aspects of this emerging clade that likely mediate differences in virulence and drug response, including different cell wall families. To begin to characterize the species-specific genes important for antifungal response, we profiled the gene expression of C. auris in response to voriconazole and amphotericin B and found induction of several transporters and metabolic regulators that may play a role in drug resistance. Together, this study provides a comprehensive view of the genomic basis of drug resistance, potential for mating, and virulence in this emerging fungal clade.
| Type: | Working / discussion paper |
|---|---|
| Title: | Genomic basis of multidrug-resistance, mating, and virulence in Candida auris and related emerging species |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1101/299917 |
| Publisher version: | https://doi.org/10.1101/299917 |
| Language: | English |
| Additional information: | This version is the author accepted manuscript. For information on re-use, please refer to the publisher’s terms and conditions. |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences |
| URI: | https://discovery-pp.ucl.ac.uk/id/eprint/10052930 |
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