Journal
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY
Volume 63, Issue 1, Pages -Publisher
AMER SOC MICROBIOLOGY
DOI: 10.1128/AAC.01811-18
Keywords
Candida auris; ERG11; FKS; azole; echinocandin; molecular beacons; resistance
Categories
Funding
- CDC's investments to combat antibiotic resistance [200-2017-96195 (BAA FY2017-OADS-01)]
- China Scholarship Council (CSC) [201706210414]
- U.S. National Institutes of Health
- Astellas Pharma (Reference Center for Molecular Evaluation of Drug Resistance to Echinocandin and Triazole Antifungal Drugs)
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Candida auris is an emerging multidrug-resistant yeast that can cause serious invasive infections. The accurate and rapid assessment of antifungal resistance is important for effective patient management. A novel and highly accurate diagnostic platform was established for the rapid identification of ERG11 mutations conferring azole resistance and FKS1 mutations associated with echinocandin resistance in C. auris. Using allele-specific molecular beacons and DNA melting curve analysis following asymmetric PCR, a duplex ERG11 assay and a simplex FKS1 HS1 assay were developed to identify the most prominent resistance-associated mutations (Y132F and K143R in ERG11; S639F in FKS1 HS1) within 2 h. Assays were validated by testing a panel of 94 C. auris clinical isolates in a blind manner. The molecular diagnostic results from the assays were 100% concordant with DNA sequencing results. This platform has the potential to overcome the deficiencies of existing in vitro susceptibility-based assays to identify azole-and/or echinocandin-resistant C. auris, and thus, it holds promise as a surrogate diagnostic method to direct antifungal therapy more effectively.
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