Antifungal activity of promethazine and chlorpromazine against planktonic cells and biofilms of Cryptococcus neoformans/Cryptococcus gattii complex species. (3rd February 2020)

• Record Type: Journal Article
• Authors: 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
• Is Part Of: Medical mycology. Volume 58:Number 7(2020)
• Page Start: 906
• Page End: 912
• Publication Date: 2020-02-03
• Subjects: Cryptococcus spp -- phenothiazines -- antifungal -- planktonic -- biofilm; Medical mycology -- Periodicals; Veterinary mycology -- Periodicals; Mycology -- Periodicals; Mycoses -- Periodicals; Pathogenic fungi -- Periodicals; 616.969005
• DOI: 10.1093/mmy/myz140
• Languages: English
• ISSNs: 1369-3786

Abstract

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.