Cited by 80Antifungal resistance and susceptibilityFungal and yeast genetics researchFungal Plant Pathogen Control

The Synergistic Effect of Azoles and Fluoxetine against Resistant Candida albicans Strains Is Attributed to Attenuating Fungal Virulence

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Gu, Wenrui, Guo, Dongmei, Zhang, Liuping, Xu, Dongmei, Sun, Shujuan·2016·Antimicrobial Agents and Chemotherapy

Abstract

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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Crossref · 10.1128/aac.03046-15

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Authors
Gu, W., Guo, D., Zhang, L., Xu, D., & Sun, S.
Affiliations
  • Shandong University (CN)
  • Taishan Medical University (CN)
Venue
Antimicrobial Agents and Chemotherapy
Published
2016-10
Volume
60
Issue
10
Pages
6179-6188
ISSN
  • 0066-4804 (ISSN-L)
  • 1098-6596
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
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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