Antifungal activity of selective serotonin reuptake inhibitors against Cryptococcus spp. and their possible mechanism of action
Copyright © 2023 SFMM. Published by Elsevier Masson SAS. All rights reserved..
Fungal infections caused by Cryptococcus spp. pose a threat to health, especially in immunocompromised individuals. The available arsenal of drugs against cryptococcosis is limited, due to their toxicity and/or lack of accessibility in low-income countries, requiring more therapeutic alternatives. Selective serotonin reuptake inhibitors (SSRIs), through drug repositioning, are a promising alternative to broaden the range of new antifungals against Cryptococcus spp. This study evaluates the antifungal activity of three SSRIs, sertraline, paroxetine, and fluoxetine, against Cryptococcus spp. strains, as well as assesses their possible mechanism of action. Seven strains of Cryptococcus spp. were used. Sensitivity to SSRIs, fluconazole, and itraconazole was evaluated using the broth microdilution assay. The interactions resulting from combinations of SSRIs and azoles were investigated using the checkerboard assay. The possible action mechanism of SSRIs against Cryptococcus spp. was evaluated through flow cytometry assays. The SSRIs exhibited in vitro antifungal activity against Cryptococcus spp. strains, with minimum inhibitory concentrations ranging from 2 to 32 μg/mL, and had synergistic and additive interactions with azoles. The mechanism of action of SSRIs against Cryptococcus spp. involved damage to the mitochondrial membrane and increasing the production of reactive oxygen species, resulting in loss of cellular viability and apoptotic cell death. Fluoxetine also was able to cause significant damage to yeast DNA. These findings demonstrate the in vitro antifungal potential of SSRIs against Cryptococcus spp. strains.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2023 |
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| Erschienen: |
2023 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:33 |
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| Enthalten in: |
Journal de mycologie medicale - 33(2023), 4 vom: 15. Nov., Seite 101431 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
da Silva, Cecília Rocha [VerfasserIn] |
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| Links: |
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| Themen: |
01K63SUP8D |
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| Anmerkungen: |
Date Completed 13.11.2023 Date Revised 15.02.2024 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1016/j.mycmed.2023.101431 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM361637357 |
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| 245 | 1 | 0 | |a Antifungal activity of selective serotonin reuptake inhibitors against Cryptococcus spp. and their possible mechanism of action |
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| 520 | |a Copyright © 2023 SFMM. Published by Elsevier Masson SAS. All rights reserved. | ||
| 520 | |a Fungal infections caused by Cryptococcus spp. pose a threat to health, especially in immunocompromised individuals. The available arsenal of drugs against cryptococcosis is limited, due to their toxicity and/or lack of accessibility in low-income countries, requiring more therapeutic alternatives. Selective serotonin reuptake inhibitors (SSRIs), through drug repositioning, are a promising alternative to broaden the range of new antifungals against Cryptococcus spp. This study evaluates the antifungal activity of three SSRIs, sertraline, paroxetine, and fluoxetine, against Cryptococcus spp. strains, as well as assesses their possible mechanism of action. Seven strains of Cryptococcus spp. were used. Sensitivity to SSRIs, fluconazole, and itraconazole was evaluated using the broth microdilution assay. The interactions resulting from combinations of SSRIs and azoles were investigated using the checkerboard assay. The possible action mechanism of SSRIs against Cryptococcus spp. was evaluated through flow cytometry assays. The SSRIs exhibited in vitro antifungal activity against Cryptococcus spp. strains, with minimum inhibitory concentrations ranging from 2 to 32 μg/mL, and had synergistic and additive interactions with azoles. The mechanism of action of SSRIs against Cryptococcus spp. involved damage to the mitochondrial membrane and increasing the production of reactive oxygen species, resulting in loss of cellular viability and apoptotic cell death. Fluoxetine also was able to cause significant damage to yeast DNA. These findings demonstrate the in vitro antifungal potential of SSRIs against Cryptococcus spp. strains | ||
| 650 | 4 | |a Journal Article | |
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| 700 | 1 | |a Ferreira, Thais Lima |e verfasserin |4 aut | |
| 700 | 1 | |a Leitão, Amanda Cavalcante |e verfasserin |4 aut | |
| 700 | 1 | |a de Farias Cabral, Vitória Pessoa |e verfasserin |4 aut | |
| 700 | 1 | |a Rodrigues, Daniel Sampaio |e verfasserin |4 aut | |
| 700 | 1 | |a Barbosa, Amanda Dias |e verfasserin |4 aut | |
| 700 | 1 | |a Moreira, Lara Elloyse Almeida |e verfasserin |4 aut | |
| 700 | 1 | |a Filho, Hugo Leonardo Pereira |e verfasserin |4 aut | |
| 700 | 1 | |a de Andrade Neto, João Batista |e verfasserin |4 aut | |
| 700 | 1 | |a Rios, Maria Erivanda França |e verfasserin |4 aut | |
| 700 | 1 | |a Cavalcanti, Bruno Coêlho |e verfasserin |4 aut | |
| 700 | 1 | |a Magalhães, Hemerson Iury Ferreira |e verfasserin |4 aut | |
| 700 | 1 | |a de Moraes, Manoel Odorico |e verfasserin |4 aut | |
| 700 | 1 | |a Vitoriano Nobre, Hélio |e verfasserin |4 aut | |
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