The Synergistic Effect of Azoles and Fluoxetine against Resistant Candida albicans Strains Is Attributed to Attenuating Fungal Virulence
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This study evaluated the synergistic effects of the selective serotonin reuptake inhibitor, fluoxetine, in combination with azoles against Candida albicans both in vitro and in vivo and explored the underlying mechanism. MICs, sessile MICs, and time-kill curves were determined for resistant C. albicans . Galleria mellonella was used as a nonvertebrate model for determining the efficacy of the drug combinations against C. albicans in vivo . For the mechanism study, gene expression levels of the SAP gene family were determined by reverse transcription (RT)-PCR, and extracellular phospholipase activities were detected in vitro by the egg yolk agar method. The combinations resulted in synergistic activity against C. albicans strains, but the same effect was not found for the non- albicans Candida strains. For the biofilms formed over 4, 8, and 12 h, synergism was seen for the combination of fluconazole and fluoxetine. In addition, the time-kill curves confirmed the synergism dynamically. The results of the G. mellonella studies agreed with the in vitro analysis. In the mechanism study, we observed that fluconazole plus fluoxetine caused downregulation of the gene expression levels of SAP1 to SAP4 and weakened the extracellular phospholipase activities of resistant C. albicans . The combinations of azoles and fluoxetine showed synergistic effects against resistant C. albicans may diminish the virulence properties of C. albicans .
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Microdilution checkerboard assays were utilized, and the ΣFICI was calculated and interpreted as previously described.
“To evaluate the in vitro effectiveness of the AmB/LNP combination against a variety of Candida species, microdilution checkerboard assays were utilized, and the ΣFICI was calculated and interpreted as previously described [26,27].”
From Lansoprazole interferes with fungal respiration and acts synergistically with amphotericin B against multidrug-resistant <i>Candida auris</i> (2024) · cites this paper as [26]
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Self-citation
- Authors
- Gu, W., Guo, D., Zhang, L., Xu, D., & Sun, S.
- Affiliations
- Shandong University (CN)
- Taishan Medical University (CN)
- Venue
- Antimicrobial Agents and Chemotherapy
- Publisher
- American Society for Microbiology
- Published
- 2016-10
- Volume
- 60
- Issue
- 10
- Pages
- 6179-6188
- ISSN
- 0066-4804 (ISSN-L)
- 1098-6596
- PMC
- PMC5038273
- OpenAlex
- W2521603595
- Cited by
- 80
- References
- 48
- Citations by year
- 2026: 4 · 2025: 8 · 2024: 7 · 2023: 8 · 2022: 5 · 2021: 8 · 2020: 14 · 2019: 9 · 2018: 7 · 2017: 8 · 2016: 1 · 2015: 1
- FWCI
- 7.69
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Antimicrobial Agents and Chemotherapy (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Shandong Provincial Natural Science Foundation (ZR2011HL049)
- Department of Science and Technology of Shandong Province (2013GSF11848)
- Topics
- Health Sciences › Medicine › Infectious Diseases › Antifungal resistance and susceptibility
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Fungal and yeast genetics research
- Life Sciences › Agricultural and Biological Sciences › Ecology, Evolution, Behavior and Systematics › Fungal Plant Pathogen Control
- Keywords
- Candida albicans, fluoxetine, azoles, fluconazole, antifungal synergy, antifungal resistance, fungal virulence, biofilm, Galleria mellonella model, time-kill kinetics, non-albicans Candida
- MeSH terms
- Animals, Antifungal Agents, Azoles, Candida albicans, Drug Evaluation, Preclinical, Drug Synergism, Fluoxetine, Fungal Proteins, Larva, Microbial Sensitivity Tests, Moths, Phospholipases, Virulence, Aspartic Acid Endopeptidases, Selective Serotonin Reuptake Inhibitors, Biofilms, Drug Resistance, Fungal
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