1. In vitro anti-Candida activity of selective serotonin reuptake inhibitors against fluconazole-resistant strains and their activity against biofilm-forming isolates.
- Author
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Costa Silva RA, da Silva CR, de Andrade Neto JB, da Silva AR, Campos RS, Sampaio LS, do Nascimento FBSA, da Silva Gaspar B, da Cruz Fonseca SG, Josino MAA, Grangeiro TB, Gaspar DM, de Lucena DF, de Moraes MO, Cavalcanti BC, and Nobre Júnior HV
- Subjects
- Animals, Apoptosis drug effects, Biofilms growth & development, Candida cytology, Candida genetics, Candida growth & development, Cell Count, Cell Death drug effects, Cell Line, Cell Proliferation drug effects, DNA Damage drug effects, DNA, Fungal drug effects, Fibroblasts microbiology, Flow Cytometry, In Vitro Techniques, Membrane Potentials, Mice, Microbial Sensitivity Tests, Microbial Viability drug effects, Mitochondrial Membranes drug effects, Paroxetine pharmacology, Plasma drug effects, Selective Serotonin Reuptake Inhibitors administration & dosage, Sertraline pharmacology, Antifungal Agents pharmacology, Biofilms drug effects, Candida drug effects, Drug Resistance, Fungal drug effects, Fluconazole pharmacology, Selective Serotonin Reuptake Inhibitors pharmacology
- Abstract
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., (Copyright © 2017 Elsevier Ltd. All rights reserved.)
- Published
- 2017
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