Rapid Detection of FKS -Associated Echinocandin Resistance in Candida glabrata

Zhao, Yanan; Nagasaki, Yoji; Kordalewska, Milena; Press, Ellen G.; Shields, Ryan K.; Nguyen, M. Hong; Clancy, Cornelius J.; Perlin, David S.

doi:10.1128/aac.01574-16

Cited by 61Antifungal resistance and susceptibilityFungal Plant Pathogen ControlFungal and yeast genetics research

Rapid Detection of FKS -Associated Echinocandin Resistance in Candida glabrata

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Zhao, Yanan, Nagasaki, Yoji, Kordalewska, Milena, Press, Ellen G., Shields, Ryan K., Nguyen, M. Hong, Clancy, Cornelius J., Perlin, David S.·2016·Antimicrobial Agents and Chemotherapy

DOI 10.1128/aac.01574-16PMC PMC5075061

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Abstract

A novel and highly accurate diagnostic assay platform was established for rapid identification of FKS mutations associated with echinocandin resistance in Candida glabrata . The assay platform uses allele-specific molecular beacon and DNA melt analysis following asymmetric PCR. A dual assay for FKS1 and FKS2 was developed to identify within 3 h the most common and clinically relevant resistance-associated mutations, including 8 FKS1 HS1 (wild type [WT], S629P, F625S, D632Y, D632E [T1896G], D632E [T1896A], I634V, and F625F) and 7 FKS2 HS1 (WT, F659del, F659S, F659V, F659L, S663P, and S663F) genotypes. A blinded panel of 188 C. glabrata clinical isolates was tested by both assays. The molecular diagnostic results from the dual assay were 100% concordant with data obtained from DNA sequencing. This platform has the potential to overcome the deficiencies of existing in vitro susceptibility-based assays to identify echinocandin-resistant C. glabrata and holds promise as a surrogate diagnostic method to better direct echinocandin therapy.

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12 out of 59 (20.34%) descendant strains carry proved clinically significant FKS2 point mutations, including F659del, F659S, F659C, and S663F.
“12 out of 59 (20.34%) descendant strains carry proved clinically significant FKS2 point mutations, including F659del, F659S, F659C, and S663F [38, 39, 40].”
From Calcineurin‐Dependent Stress Adaptation Enables Caspofungin Heteroresistance Leading to Stable Resistance in Candida Glabrata (2026) · cites this paper as [38]
The Results report F659del, F659S, and S663F among the FKS2 alterations detected in clinical isolates. They do not report F659C or a cohort of 59 descendant strains, and their counts do not establish 12 of 59 (20.34%). F659del is a deletion, not a point mutation. (LLM, conf=0.88)
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The FKS2 F659del mutation has been reported to contribute to elevated echinocandin MICs.
“This specific mutation has also been reported for its contribution to elevated echinocandin MICs [38, 41].”
From Calcineurin‐Dependent Stress Adaptation Enables Caspofungin Heteroresistance Leading to Stable Resistance in Candida Glabrata (2026) · cites this paper as [38]

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“%) descendant strains carry proved clinically significant FKS2 point mutations, including F659del , F659S , F659C , and S663F [ 38–40 ].”
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Authors: Zhao, Y., Nagasaki, Y., Kordalewska, M., Press, E. G., Shields, R. K., Nguyen, M. H., Clancy, C. J., & Perlin, D. S.
Affiliations: Rutgers Health (US)
University of Pittsburgh (US)
ORCID: Zhao, Yanan
Kordalewska, Milena
Shields, Ryan K.
Nguyen, M. Hong
Clancy, Cornelius J.
Perlin, David S.
Venue: Antimicrobial Agents and Chemotherapy
Publisher: American Society for Microbiology
Published: 2016-11
Volume: 60
Issue: 11
Pages: 6573-6577
ISSN: 0066-4804 (ISSN-L)
1098-6596
DOI: 10.1128/aac.01574-16
PMC: PMC5075061
OpenAlex: W2507370632
Cited by: 61
References: 25
Citations by year: 2026: 3 · 2025: 3 · 2023: 4 · 2022: 2 · 2021: 11 · 2020: 6 · 2019: 13 · 2018: 7 · 2017: 10 · 2016: 2
FWCI: 7.97
Type: journal article
Language: en
Open access: green
www.ncbi.nlm.nih.gov
Licence: journals.asm.org/non-commercial-tdm-license (tdm)
Locations: Antimicrobial Agents and Chemotherapy (publishedVersion)
PubMed Central (publishedVersion)
PubMed (publishedVersion)
Funders: NIH (R01AI109025, K08AI114883)
Merck (53563)
Topics: Health Sciences › Medicine › Infectious Diseases › Antifungal resistance and susceptibility
Life Sciences › Agricultural and Biological Sciences › Ecology, Evolution, Behavior and Systematics › Fungal Plant Pathogen Control
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Fungal and yeast genetics research
Keywords: Candida glabrata, echinocandin resistance, FKS1, FKS2, molecular beacons, asymmetric PCR, rapid diagnostic tests, antifungal resistance, clinical isolates, echinocandin therapy
MeSH terms: Alleles, Antifungal Agents, Candidiasis, DNA, Fungal, Fungal Proteins, Glucosyltransferases, Humans, Isoenzymes, Microbial Sensitivity Tests, Mutation, Nucleic Acid Denaturation, Sensitivity and Specificity, Molecular Probes, Gene Expression, Polymerase Chain Reaction, Drug Resistance, Fungal, Candida glabrata, Echinocandins

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Rapid Detection of FKS -Associated Echinocandin Resistance in Candida glabrata

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