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Rapid Detection of ERG11-Associated Azole Resistance and FKS-Associated Echinocandin Resistance in Candida auris.

Abstract

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.

Authors+Show Affiliations

Public Health Research Institute, New Jersey Medical School, Rutgers Biomedical and Health Sciences, Newark, New Jersey, USA. Department of Clinical Laboratory, Beijing Key Laboratory for Mechanisms Research and Precision Diagnosis of Invasive Fungal Diseases (BZ0447), Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, China.Public Health Research Institute, New Jersey Medical School, Rutgers Biomedical and Health Sciences, Newark, New Jersey, USA.Public Health Research Institute, New Jersey Medical School, Rutgers Biomedical and Health Sciences, Newark, New Jersey, USA.Public Health Research Institute, New Jersey Medical School, Rutgers Biomedical and Health Sciences, Newark, New Jersey, USA.Public Health Research Institute, New Jersey Medical School, Rutgers Biomedical and Health Sciences, Newark, New Jersey, USA perlinds@njms.rutgers.edu zhaoy1@njms.rutgers.edu.Public Health Research Institute, New Jersey Medical School, Rutgers Biomedical and Health Sciences, Newark, New Jersey, USA perlinds@njms.rutgers.edu zhaoy1@njms.rutgers.edu.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

30397051

Citation

Hou, Xin, et al. "Rapid Detection of ERG11-Associated Azole Resistance and FKS-Associated Echinocandin Resistance in Candida Auris." Antimicrobial Agents and Chemotherapy, vol. 63, no. 1, 2019.
Hou X, Lee A, Jiménez-Ortigosa C, et al. Rapid Detection of ERG11-Associated Azole Resistance and FKS-Associated Echinocandin Resistance in Candida auris. Antimicrob Agents Chemother. 2019;63(1).
Hou, X., Lee, A., Jiménez-Ortigosa, C., Kordalewska, M., Perlin, D. S., & Zhao, Y. (2019). Rapid Detection of ERG11-Associated Azole Resistance and FKS-Associated Echinocandin Resistance in Candida auris. Antimicrobial Agents and Chemotherapy, 63(1), doi:10.1128/AAC.01811-18.
Hou X, et al. Rapid Detection of ERG11-Associated Azole Resistance and FKS-Associated Echinocandin Resistance in Candida Auris. Antimicrob Agents Chemother. 2019;63(1) PubMed PMID: 30397051.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Rapid Detection of ERG11-Associated Azole Resistance and FKS-Associated Echinocandin Resistance in Candida auris. AU - Hou,Xin, AU - Lee,Annie, AU - Jiménez-Ortigosa,Cristina, AU - Kordalewska,Milena, AU - Perlin,David S, AU - Zhao,Yanan, Y1 - 2018/12/21/ PY - 2018/08/24/received PY - 2018/10/23/accepted PY - 2018/11/7/pubmed PY - 2020/1/15/medline PY - 2018/11/7/entrez KW - Candida auris KW - ERG11 KW - FKS KW - azole KW - echinocandin KW - molecular beacons KW - resistance JF - Antimicrobial agents and chemotherapy JO - Antimicrob. Agents Chemother. VL - 63 IS - 1 N2 - 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. SN - 1098-6596 UR - https://www.unboundmedicine.com/medline/citation/30397051/Rapid_Detection_of_ERG11_Associated_Azole_Resistance_and_FKS_Associated_Echinocandin_Resistance_in_Candida_auris_ L2 - http://aac.asm.org/cgi/pmidlookup?view=long&pmid=30397051 DB - PRIME DP - Unbound Medicine ER -