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Antimicrob Agents Chemother DOI:10.1128/AAC.01466-20

Experimental Evolution Identifies Adaptive Aneuploidy as a Mechanism of Fluconazole Resistance in Candida auris.

Publication TypeJournal Article
Year of Publication2020
AuthorsBing, J, Hu, T, Zheng, Q, Muñoz, JF, Cuomo, CA, Huang, G
JournalAntimicrob Agents Chemother
Volume65
Issue1
Date Published2020 12 16
ISSN1098-6596
KeywordsAneuploidy, Antifungal Agents, Candida, Drug Resistance, Fungal, Fluconazole, Humans, Microbial Sensitivity Tests
Abstract

is a newly emerging fungal pathogen of humans and has attracted considerable attention from both the clinical and basic research communities. Clinical isolates of are often resistant to one or more antifungal agents. To explore how antifungal resistance develops, we performed experimental evolution assays using a fluconazole-susceptible isolate of (BJCA001). After a series of passages through medium containing increasing concentrations of fluconazole, fungal cells acquired resistance. By sequencing and comparing the genomes of the parental fluconazole-susceptible strain and 26 experimentally evolved strains of , we found that a portion of fluconazole-resistant strains carried one extra copy of chromosome V. In the absence of fluconazole, cells rapidly became susceptible and lost the extra copy of chromosome V. Genomic and transcriptome sequencing (RNA-Seq) analyses indicate that this chromosome carries a number of drug resistance-related genes, which were transcriptionally upregulated in the resistant, aneuploid strains. Moreover, missense mutations were identified in the genes , , and in all experimentally evolved strains. Our findings suggest that the gain of an extra copy of chromosome V is associated with the rapid acquisition of fluconazole resistance and may represent an important evolutionary mechanism of antifungal resistance in .

DOI10.1128/AAC.01466-20
Pubmed

https://www.ncbi.nlm.nih.gov/pubmed/33077664?dopt=Abstract

Alternate JournalAntimicrob Agents Chemother
PubMed ID33077664
PubMed Central IDPMC7927865