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FKS Mutations and Elevated Echinocandin MIC Values among Candida glabrata Isolates from U.S. Population-Based Surveillance
Open accessAbstract
Candida glabrata is the second leading cause of candidemia in the United States. Its high-level resistance to triazole antifungal drugs has led to the increased use of the echinocandin class of antifungal agents for primary therapy of these infections. We monitored C. glabrata bloodstream isolates from a population-based surveillance study for elevated echinocandin MIC values (MICs of ≥0.25 μg/ml). From the 490 C. glabrata isolates that were screened, we identified 16 isolates with an elevated MIC value (2.9% of isolates from Atlanta and 2.0% of isolates from Baltimore) for one or more of the echinocandin drugs caspofungin, anidulafungin, and micafungin. All of the isolates with elevated MIC values had a mutation in the previously identified hot spot 1 of either the glucan synthase FKS1 (n = 2) or FKS2 (n = 14) gene. No mutations were detected in hot spot 2 of either FKS1 or FKS2. The predominant mutation was mutation of FKS2-encoded serine 663 to proline (S663P), found in 10 of the isolates with elevated echinocandin MICs. Two of the mutations, R631G for FKS1 and R665G for FKS2, have not been reported previously for C. glabrata. Multilocus sequence typing indicated that the predominance of the S663P mutation was not due to the clonal spread of a single sequence type. With a rising number of echinocandin therapy failures reported, it is important to continue to monitor rates of elevated echinocandin MIC values and the associated mutations.
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“We discovered non-synonymous changes in MOH1 in two out of the 10 clinical isolates sequenced and non-synonymous changes in CDC6 in 7 out of 10 of the clinical isolates (Figure 4).”
From Global Analysis of the Evolution and Mechanism of Echinocandin Resistance in Candida glabrata (2012) · cites this paper as [71]
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In the citing paper
“We discovered non-synonymous changes in MOH1 in two out of the 10 clinical isolates sequenced and non-synonymous changes in CDC6 in 7 out of 10 of the clinical isolates (Figure 4).”
From Global Analysis of the Evolution and Mechanism of Echinocandin Resistance in Candida glabrata (2012) · cites this paper as [71]
Experimental — accuracy not yet measuredIn the citing paper
“Alternative technologies are being developed including molecular detection and MALDI-TOF.”
From Echinocandin resistance: an emerging clinical problem? (2014) · cites this paper as [53]
In the citing paper
“Categorizations determined using MALDI-TOF MS-based AFST (ms-AFST) were consistent with the wild-type and mutant FKS1 genotypes and the AFST reference methodology.”
From Echinocandin resistance: an emerging clinical problem? (2014) · cites this paper as [53]
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“It was followed by a simplified version, which facilitated discrimination of susceptible and resistant isolates of C. albicans after only 3 hours of incubation in the presence of two “breakpoint” level drug concentrations (0.03 and 32 mg/L) of caspofungin (53).”
From Echinocandin resistance: an emerging clinical problem? (2014) · cites this paper as [53]
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“FKS Mutations and Elevated Echinocandin MIC Values among Candida glabrata Isolates from U.S. Population-Based Surveillance Alicia J. Zimbeck,1 Naureen Iqbal,1 Angela M. Ahlquist,1,2 Monica M. Farley,3,4 Lee H. Harrison,5 Tom Chiller,1 and Shawn R. Lockhart1* Mycotic Disease Branch, Centers for Disease Control and Prev…”
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Gonzalez-Jimenez, I., Keniya, M. V., Aptekmann, A. A., Quinteros, C., Wilkerson, A., Arastehfar, A., Daneshnia, F., Perlin, D. S., & Shor, E. (2025) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.00500-25 · Cited by 4
Metadata
- Authors
- Zimbeck, A. J., Iqbal, N., Ahlquist, A. M., Farley, M. M., Harrison, L. H., Chiller, T., & Lockhart, S. R.
- Affiliations
- Centers for Disease Control and Prevention (US)
- Emory University (US)
- Johns Hopkins University (US)
- Venue
- Antimicrobial Agents and Chemotherapy
- Publisher
- American Society for Microbiology
- Published
- 2010-12
- Volume
- 54
- Issue
- 12
- Pages
- 5042-5047
- ISSN
- 0066-4804 (ISSN-L)
- 1098-6596
- PMC
- PMC2981257
- OpenAlex
- W2146779308
- Cited by
- 136
- References
- 38
- Citations by year
- 2026: 4 · 2025: 9 · 2024: 2 · 2023: 4 · 2022: 2 · 2021: 8 · 2020: 9 · 2019: 5 · 2018: 11 · 2017: 10 · 2016: 12 · 2015: 9 · 2014: 16 · 2013: 7 · 2012: 18
- FWCI
- 7.23
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Antimicrobial Agents and Chemotherapy (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Association of Public Health Laboratories
- Centers for Disease Control and Prevention
- Topics
- Health Sciences › Medicine › Infectious Diseases › Antifungal resistance and susceptibility
- Life Sciences › Agricultural and Biological Sciences › Plant Science › 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, caspofungin, anidulafungin, micafungin, candidemia, bloodstream isolates, antifungal susceptibility, multilocus sequence typing, population-based surveillance
- MeSH terms
- Caspofungin, Micafungin, Anidulafungin, Antifungal Agents, Candidiasis, Fungal Proteins, Glucosyltransferases, Microbial Sensitivity Tests, Mutation, Polymerase Chain Reaction, Drug Resistance, Multiple, Fungal, Candida glabrata, Echinocandins, Lipopeptides
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