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Overexpression of Candida albicans CDR1,CDR2, or MDR1 Does Not Produce Significant Changes in Echinocandin Susceptibility
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The micafungin and caspofungin susceptibilities of Candida albicans laboratory and clinical isolates and of Saccharomyces cerevisiae strains stably hyperexpressing fungal ATP-binding cassette (ABC) or major facilitator superfamily (MFS) transporters involved in azole resistance were determined using three separate methods. Yeast strains hyperexpressing individual alleles of ABC transporters or an MFS transporter from C. albicans gave the expected resistance profiles for the azoles fluconazole, itraconazole, and voriconazole. The strains hyperexpressing CDR2 showed slightly decreased susceptibility to caspofungin in agar plate drug resistance assays, as previously reported, but increased susceptibility to micafungin compared with either the strains hyperexpressing CDR1 or the null parent deleted of seven ABC transporters. The strains hyperexpressing CDR1 showed slightly decreased susceptibility to micafungin in these assays. A C. albicans clinical isolate overexpressing both Cdr1p and Cdr2p relative to its azole-sensitive isogenic progenitor acquired resistance to azole drugs and showed reduced susceptibility to caspofungin and slightly increased susceptibility to micafungin in agar plate drug resistance assays. None of the strains showed significant resistance to micafungin or caspofungin in liquid microdilution susceptibility assays. The antifungal activities of micafungin and caspofungin were similar in agarose diffusion assays, although the shape and size of the caspofungin inhibitory zones were affected by medium composition. The assessment of micafungin and caspofungin potency is therefore assay dependent; the differences seen with agar plate drug resistance assays occur over narrow ranges of echinocandin concentrations and are not of clinical significance.
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“Triazole-resistant clinical isolates (Pfaller et al., 2005; Messer et al., 2006) and laboratory strains (Niimi et al., 2006) that demonstrate increased drug efflux pump expression remain susceptible to the echinocandins in laboratory liquid assays.”
From Genetic Drivers of Multidrug Resistance in Candida glabrata (2016) · cites this paper as Niimi et al., 2006
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Metadata
- Authors
- Niimi, K., Maki, K., Ikeda, F., Holmes, A. R., Lamping, E., Niimi, M., Monk, B. C., & Cannon, R. D.
- Affiliations
- University of Otago (NZ)
- Astellas Pharma (Japan) (JP)
- National Institute of Infectious Diseases (JP)
- Venue
- Antimicrobial Agents and Chemotherapy
- Publisher
- American Society for Microbiology
- Published
- 2006-04
- Volume
- 50
- Issue
- 4
- Pages
- 1148-1155
- ISSN
- 0066-4804 (ISSN-L)
- 1098-6596
- PMC
- PMC1426986
- OpenAlex
- W2120702660
- Cited by
- 134
- References
- 37
- Citations by year
- 2025: 7 · 2024: 2 · 2023: 6 · 2022: 2 · 2021: 10 · 2020: 4 · 2019: 4 · 2018: 4 · 2017: 14 · 2016: 10 · 2015: 8 · 2014: 5 · 2013: 4 · 2012: 9
- FWCI
- 7.54
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Antimicrobial Agents and Chemotherapy (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Japan Health Sciences Foundation
- Astellas Pharma
- Astellas Foundation for Research on Metabolic Disorders
- National Institutes of Health
- National Institute of Dental and Craniofacial Research (R21DE015075)
- Topics
- Health Sciences › Medicine › Infectious Diseases › Antifungal resistance and susceptibility
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Fungal and yeast genetics research
- Health Sciences › Medicine › Oncology › Drug Transport and Resistance Mechanisms
- Keywords
- Candida albicans, echinocandin susceptibility, micafungin, caspofungin, CDR1, CDR2, MDR1, ABC transporters, major facilitator superfamily, azole resistance, antifungal susceptibility testing, clinical isolates
- MeSH terms
- Caspofungin, Micafungin, Antifungal Agents, Candida albicans, Diffusion, Fungal Proteins, Lipoproteins, Microbial Sensitivity Tests, Peptides, Cyclic, ATP-Binding Cassette Transporters, Genes, MDR, Drug Resistance, Fungal, Membrane Transport Proteins, Echinocandins, Lipopeptides
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