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Updated: Jun 26, 2026
Automated Measurement of Cryptococcal Species Polysaccharide Capsule and Cell Body
Published on: January 11, 2018
In vitro effects of selective serotonin reuptake inhibitors on Cryptococcus gattii capsule and biofilm
Letícia Rampazzo da Gama Viveiro1, Amanda Rodrigues Rehem1, Evelyn Luzia De Souza Santos1
1Department of Biosciences and Oral Diagnosis, Institute of Science and Technology, São Paulo State University (UNESP), São Paulo 12245-000, Brazil.
Abstract:
Infections caused by Cryptococcus gattii mainly affect immunocompetent individuals and the treatment presents important limitations. This study aimed to validate the efficacy of selective serotonin reuptake inhibitors (SSRI), fluoxetine hydrochloride (FLH), and paroxetine hydrochloride (PAH) in vitro against C. gattii. The antifungal activity of SSRI using the microdilution method revealed a minimal inhibitory concentration (MIC) of 31.25 µg/ml. The combination of FLH or PAH with amphotericin B (AmB) was analyzed using the checkerboard assay and the synergistic effect of SSRI in combination with AmB was able to reduce the SSRI or AmB MIC values 4-8-fold. When examining the effect of SSRI on the induced capsules, we observed that FLH and PAH significantly decreased the size of C. gattii capsules. In addition, the effects of FLH and PAH were evaluated in biofilm biomass and viability. The SSRI were able to reduce biofilm biomass and biofilm viability. In conclusion, our results indicate the use of FLH and PAH exhibited in vitro anticryptococcal activity, representing a possible future alternative for the cryptococcosis treatment.
Insights
Selective serotonin reuptake inhibitors (SSRIs), fluoxetine and paroxetine, show in vitro antifungal activity against Cryptococcus gattii. These SSRIs also reduced fungal capsule size and biofilm formation, suggesting potential new treatments for cryptococcosis.
Area of Science:
- Mycology
- Pharmacology
- Infectious Diseases
Background:
- Cryptococcus gattii infections primarily impact immunocompetent individuals.
- Current treatments for C. gattii infections have significant limitations.
- Selective serotonin reuptuptake inhibitors (SSRIs) are commonly used antidepressants.
Purpose of the Study:
- To evaluate the in vitro efficacy of SSRIs, specifically fluoxetine hydrochloride (FLH) and paroxetine hydrochloride (PAH), against C. gattii.
- To investigate the synergistic effects of SSRIs in combination with amphotericin B (AmB).
- To assess the impact of SSRIs on C. gattii capsule size, biofilm formation, and viability.
Main Methods:
- Antifungal activity was determined using the microdilution method to establish minimal inhibitory concentrations (MICs).
- Checkerboard assay was employed to analyze the synergistic interactions between SSRIs and AmB.
- Capsule size, biofilm biomass, and biofilm viability were quantified to assess SSRI effects.
Main Results:
- SSRI demonstrated in vitro anticryptococcal activity with an MIC of 31.25 µg/ml.
- Combination therapy with SSRIs and AmB resulted in a 4-8 fold reduction in MIC values, indicating synergy.
- FLH and PAH significantly reduced C. gattii capsule size and inhibited biofilm biomass and viability.
Conclusions:
- Fluoxetine and paroxetine exhibit promising in vitro anticryptococcal activity against C. gattii.
- SSRI-AmB combination therapy shows synergistic potential, reducing the required concentrations of both agents.
- These findings suggest that SSRIs could represent a novel therapeutic alternative for cryptococcosis treatment.
