In vitro anti-Candida activity of selective serotonin reuptake inhibitors against fluconazole-resistant strains and their activity against biofilm-forming isolates
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Recent research has shown broad antifungal activity of the classic antidepressants selective serotonin reuptake inhibitors (SSRIs). This fact, combined with the increased cross-resistance frequency of the genre Candida regarding the main treatment today, fluconazole, requires the development of novel therapeutic strategies. In that context, this study aimed to assess the antifungal potential of fluoxetine, sertraline, and paroxetine against fluconazole-resistant Candida spp. planktonic cells, as well as to assess the mechanism of action and the viability of biofilms treated with fluoxetine. After 24 h, the fluconazole-resistant Candida spp. strains showed minimum inhibitory concentration (MIC) in the ranges of 20-160 μg/mL for fluoxetine, 10-20 μg/mL for sertraline, and 10-100.8 μg/mL for paroxetine by the broth microdilution method (M27-A3). According to our data by flow cytometry, each of the SSRIs cause fungal death after damaging the plasma and mitochondrial membrane, which activates apoptotic signaling pathways and leads to dose-dependant cell viability loss. Regarding biofilm-forming isolates, the fluoxetine reduce mature biofilm of all the species tested. Therefore, it is concluded that SSRIs are capable of inhibit the growth in vitro of Candida spp., both in planktonic form, as biofilm, inducing cellular death by apoptosis.
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Paroxetine inhibits bacterial growth at 110-282 μM (40-101 μg/mL).
“| Paroxetine (third generation of selective serotonin reuptake inhibitors) | C. albicans, E. coli, A. baumanii | 110-282 µM (40-101 µg/mL) | Inhibits cell growth; promotes mitochondrial inhibits bacterial growth. depolarization and membrane damage in yeast, | [56,58,67-69] |”
From Antimicrobial Properties of Antidepressants and Antipsychotics—Possibilities and Implications (2021) · cites this paper as [68]
Paroxetine promotes mitochondrial depolarization and membrane damage in yeast at 110-282 μM (40-101 μg/mL).
“| Paroxetine (third generation of selective serotonin reuptake inhibitors) | C. albicans, E. coli, A. baumanii | 110-282 µM (40-101 µg/mL) | Inhibits cell growth; promotes mitochondrial inhibits bacterial growth. depolarization and membrane damage in yeast, | [56,58,67-69] |”
From Antimicrobial Properties of Antidepressants and Antipsychotics—Possibilities and Implications (2021) · cites this paper as [68]
Paroxetine inhibits cell growth in C. albicans, E. coli, and A. baumanii at 110-282 μM (40-101 μg/mL).
“| Paroxetine (third generation of selective serotonin reuptake inhibitors) | C. albicans, E. coli, A. baumanii | 110-282 µM (40-101 µg/mL) | Inhibits cell growth; promotes mitochondrial inhibits bacterial growth. depolarization and membrane damage in yeast, | [56,58,67-69] |”
From Antimicrobial Properties of Antidepressants and Antipsychotics—Possibilities and Implications (2021) · cites this paper as [68]
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Self-citationRepurposing of Drugs for the Treatment of Microbial Diseases
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Drug Repurposing Identifies New Promising Treatment Options for Invasive Fungal Diseases
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REPOSICIONAMENTO DO FÁRMACO SERTRALINA PARA O TRATAMENTO DE CANDIDÍASE VULVOVAGINAL
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- Authors
- Costa Silva, R. A., da Silva, C. R., de Andrade Neto, J. B., da Silva, A. R., Campos, R. S., Sampaio, L. S., do Nascimento, F. B. S. A., da Silva Gaspar, B., da Cruz Fonseca, S. G., Josino, M. A. A., Grangeiro, T. B., Gaspar, D. M., de Lucena, D. F., de Moraes, M. O., Cavalcanti, B. C., & Nobre Júnior, H. V.
- Affiliations
- Universidade Federal do Ceará (BR)
- ORCID
- Venue
- Microbial Pathogenesis
- Publisher
- Elsevier BV
- Published
- 2017-06
- Volume
- 107
- Pages
- 341-348
- ISSN
- 0882-4010 (ISSN-L)
- OpenAlex
- W2607318997
- Cited by
- 56
- References
- 39
- Citations by year
- 2026: 3 · 2025: 5 · 2024: 5 · 2023: 10 · 2022: 6 · 2021: 7 · 2020: 11 · 2019: 6 · 2018: 2 · 2017: 1
- FWCI
- 4.23
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Microbial Pathogenesis (publishedVersion)
- PubMed (publishedVersion)
- Portuguese National Funding Agency for Science, Research and Technology (RCAAP Project by FCT) (publishedVersion)
- 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
- Physical Sciences › Chemistry › Organic Chemistry › Antimicrobial agents and applications
- Keywords
- selective serotonin reuptake inhibitors, Candida, fluconazole resistance, fluoxetine, sertraline, paroxetine, antifungal activity, biofilm, apoptosis, mitochondrial membrane damage, cell membrane damage
- MeSH terms
- Animals, Antifungal Agents, Candida, Cell Count, Cell Line, DNA Damage, DNA, Fungal, Fibroblasts, Flow Cytometry, Membrane Potentials, Microbial Sensitivity Tests, Plasma, Fluconazole, Cell Death, Apoptosis, Selective Serotonin Reuptake Inhibitors, Paroxetine, Biofilms, Sertraline, Drug Resistance, Fungal, Cell Proliferation, Microbial Viability, Mitochondrial Membranes, Mice, In Vitro Techniques
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