Antifungal activity of promethazine and chlorpromazine against planktonic cells and biofilms of Cryptococcus neoformans/Cryptococcus gattii complex species

Abstract Cryptococcus neoformans/Cryptococcus gattii are fungal pathogens that affect the central nervous system, mainly in immunocompromised individuals. Due to the limited pharmacological arsenal available for the treatment of cryptococcosis associated with cases of antifungal resistance of Crypto...

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Veröffentlicht in:Medical mycology (Oxford) 2020-10, Vol.58 (7), p.906-912
Hauptverfasser: Brilhante, Raimunda Sâmia Nogueira, Gotay, Wilker Jose Perez, Pereira, Vandbergue Santos, de Oliveira, Jonathas Sales, Pereira-Neto, Waldemiro Aquino, Castelo-Branco, Débora de Souza Collares Maia, Cordeiro, Rossana de Aguiar, Sidrim, José Júlio Costa, Rocha, Marcos Fábio Gadelha
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container_issue 7
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container_title Medical mycology (Oxford)
container_volume 58
creator Brilhante, Raimunda Sâmia Nogueira
Gotay, Wilker Jose Perez
Pereira, Vandbergue Santos
de Oliveira, Jonathas Sales
Pereira-Neto, Waldemiro Aquino
Castelo-Branco, Débora de Souza Collares Maia
Cordeiro, Rossana de Aguiar
Sidrim, José Júlio Costa
Rocha, Marcos Fábio Gadelha
description Abstract Cryptococcus neoformans/Cryptococcus gattii are fungal pathogens that affect the central nervous system, mainly in immunocompromised individuals. Due to the limited pharmacological arsenal available for the treatment of cryptococcosis associated with cases of antifungal resistance of Cryptococcus spp. reported in some studies, the search for new compounds with antifungal potential becomes relevant. Thus, the objective of this study was to evaluate the inhibitory effect of phenothiazines (promethazine and chlorpromazine) on C. neoformans/C. gattii planktonic cells and biofilms. In vitro planktonic susceptibility testing was performed using the broth microdilution assay. The effect of phenothiazines was evaluated against biofilm formation and mature Cryptococcus biofilms. Biofilm morphology and ultrastructure were also evaluated by scanning electron microscopy. Promethazine and chlorpromazine showed antifungal activity against planktonic cells, with minimum inhibitory concentrations of 8–32 μg/ml and 4–16 μg/ml, respectively. As for biofilm formation, phenothiazines reduced biomass by 60% and metabolic activity by 90% at 64 μg/ml; while in mature biofilms, reductions of 85% and 90% in biomass and metabolic activity, respectively, were observed at 1024 μg/ml. Promethazine and chlorpromazine were also able to disrupt and fragment biofilms. In conclusion, promethazine and chlorpromazine have antifungal activity against planktonic cells and biofilms of Cryptococcus spp. These data show the potential of promethazine and chlorpromazine as antibiofilm drugs.
doi_str_mv 10.1093/mmy/myz140
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Due to the limited pharmacological arsenal available for the treatment of cryptococcosis associated with cases of antifungal resistance of Cryptococcus spp. reported in some studies, the search for new compounds with antifungal potential becomes relevant. Thus, the objective of this study was to evaluate the inhibitory effect of phenothiazines (promethazine and chlorpromazine) on C. neoformans/C. gattii planktonic cells and biofilms. In vitro planktonic susceptibility testing was performed using the broth microdilution assay. The effect of phenothiazines was evaluated against biofilm formation and mature Cryptococcus biofilms. Biofilm morphology and ultrastructure were also evaluated by scanning electron microscopy. Promethazine and chlorpromazine showed antifungal activity against planktonic cells, with minimum inhibitory concentrations of 8–32 μg/ml and 4–16 μg/ml, respectively. As for biofilm formation, phenothiazines reduced biomass by 60% and metabolic activity by 90% at 64 μg/ml; while in mature biofilms, reductions of 85% and 90% in biomass and metabolic activity, respectively, were observed at 1024 μg/ml. Promethazine and chlorpromazine were also able to disrupt and fragment biofilms. In conclusion, promethazine and chlorpromazine have antifungal activity against planktonic cells and biofilms of Cryptococcus spp. These data show the potential of promethazine and chlorpromazine as antibiofilm drugs.</description><identifier>ISSN: 1369-3786</identifier><identifier>EISSN: 1460-2709</identifier><identifier>DOI: 10.1093/mmy/myz140</identifier><identifier>PMID: 32016364</identifier><language>eng</language><publisher>England: Oxford University Press</publisher><ispartof>Medical mycology (Oxford), 2020-10, Vol.58 (7), p.906-912</ispartof><rights>The Author(s) 2020. 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As for biofilm formation, phenothiazines reduced biomass by 60% and metabolic activity by 90% at 64 μg/ml; while in mature biofilms, reductions of 85% and 90% in biomass and metabolic activity, respectively, were observed at 1024 μg/ml. Promethazine and chlorpromazine were also able to disrupt and fragment biofilms. 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source Oxford University Press Journals All Titles (1996-Current); EZB-FREE-00999 freely available EZB journals; Alma/SFX Local Collection
title Antifungal activity of promethazine and chlorpromazine against planktonic cells and biofilms of Cryptococcus neoformans/Cryptococcus gattii complex species
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