Antifungal and antibiofilm activities of selective serotonin reuptake inhibitors alone and in combination with fluconazole
Open accessAbstract
Amaç: Klinik açıdan önemli fungal patojenlerden olan Candida türleri, biyofilm üretme kapasiteleriyle tedavide zorluklara yol açmaktadır.Antifungal direnç oranları ve yeni antifungallerin keşfinin sınırlılığı göz önüne alındığında, farklı terapötik amaç için kullanılan çeşitli ilaç moleküllerinin antifungal ve antibiyofilm etkileri daha fazla önem kazanmaktadır.Çalışmamızın amacı, selektif serotonin geri alım inhibitörleri (SSRI) olan sertralin (SRT), paroksetin (PRX), fluoksetinin (FLX), tek başına ve flukonazol (FLC) ile kombine halde Candida türlerine karşı antifungal ve antibiyofilm etkilerinin belirlenmesidir.Objectives: Candida spp.are clinically important pathogens that cause difficulties for treatment by biofilm formation.Considering antifungal resistance rates and the limitations in the discovery of new antifungals, the antifungal and antibiofilm effects of various drugs used for different therapeutic purposes are becoming more important.The goal of our study was to determine the antifungal and antibiofilm effects of the selective serotonin reuptake inhibitors (SSRIs), namely sertraline (SRT), paroxetine (PRX), and fluoxetine (FLX) alone and in combination with fluconazole (FLC) against Candida spp.Materials and Methods: Twenty Candida spp.strains isolated from clinical samples from Ege University Hospital were identified by the Dalmau method and matrix-assisted laser desorption ionization time of flight mass spectrometry.The minimum inhibitory concentrations (MICs) of the SSRIs and FLC were detected by broth microdilution method.Synergistic interactions between the SSRIs and FLC were investigated by checkerboard assay.The antibiofilm effects of the SSRIs were determined by spectrophotometric microplate method.Results: Among the isolates, five different Candida spp.(C.albicans, C. glabrata, C. krusei, C. tropicalis, and C.parapsilosis) were identified.The MICs of the SSRIs ranged between 16-512 µg/mL.While SRT showed the highest antifungal effect, the antibiofilm efficacy of FLX was higher than that of the other agents.Moreover, FLX and PRX showed a synergistic effect with FLC in 13 and 19 isolates, respectively.Four isolates were strong biofilm producers while nine isolates were moderate biofilm producers.C. parapsilosis strains showed higher biofilm production than the other species.At MIC/2 concentration, FLX and SRT alone inhibited mature biofilms in six and five isolates, respectively, while PRX caused increases biofilm formation in seven isolates.Conclusion: This study revealed that MIC/2 concentrations of SSRIs could have antifungal and antibiofilm effects.SRT and FLX alone or in combination with antifungals may possibly have therapeutic potential for combating fungal infections.
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On yeast, especially C. albicans, sertraline inhibits virulence factors such as hyphal formation and secretion of aspartyl proteinases, kills yeast, and inhibits biofilm formation.
“On yeast, and especially on C. albicans, it inhibits virulence factors such as hyphal formation and the secretion of aspartyl proteinases, kills yeast, and inhibits biofilm formation.”
From Antimicrobial Properties of Antidepressants and Antipsychotics—Possibilities and Implications (2021) · cites this paper as [58]
Sertraline works synergistically with fluconazole.
“Moreover, this drug works synergistically with fluconazole [50,51,58].”
From Antimicrobial Properties of Antidepressants and Antipsychotics—Possibilities and Implications (2021) · cites this paper as [58]
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 [58]
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 [58]
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 [58]
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- Pesee S, Angkananuwat C, Tancharoensukjit S, Muanmai S, Sirivan P, Bubphawas M, Tanarerkchai N. In vitro activity of Caspofungin combined with Fluconazole on mixed Candida albicans and Candida glabrata biofilm. Med Mycol. 2016;54:384-393.
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Antimicrobial Properties of Antidepressants and Antipsychotics—Possibilities and Implications
Caldara, M., & Marmiroli, N. (2021) · Pharmaceuticals · doi:10.3390/ph14090915 · Cited by 54 · see citing works
- Authors
- TEKİNTAŞ, Y., TEMEL, A., ATEŞ, A., ERAÇ, B., METİN, D. Y., HİLMİOĞLU POLAT, S., & HOŞGÖR LİMONCU, M.
- Affiliations
- Izmir Kâtip Çelebi University (TR)
- Ege University (TR)
- ORCID
- Venue
- Turkish Journal of Pharmaceutical Sciences
- Publisher
- Galenos Yayinevi
- Published
- 2020-12-01
- Volume
- 17
- Issue
- 6
- Pages
- 667-672
- ISSN
- 1304-530X (ISSN-L)
- 2148-6247
- PMC
- PMC7786064
- OpenAlex
- W2997873762
- Cited by
- 16
- References
- 21
- Citations by year
- 2026: 4 · 2025: 2 · 2024: 1 · 2023: 5 · 2022: 2 · 2021: 2
- FWCI
- 0.30
- Type
- journal article
- Language
- en
- Open access
- diamond
- doi.org
- Locations
- Turkish Journal of Pharmaceutical Sciences (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Infectious Diseases › Antifungal resistance and susceptibility
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Bacterial biofilms and quorum sensing
- Life Sciences › Agricultural and Biological Sciences › Food Science › Essential Oils and Antimicrobial Activity
- Keywords
- selective serotonin reuptake inhibitors, fluconazole, Candida, antifungal activity, antibiofilm activity, sertraline, paroxetine, fluoxetine, drug repurposing, antifungal synergy, Candida albicans, Candida glabrata, Candida tropicalis, Candida parapsilosis, Candida krusei, antifungal resistance
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