Journal of applied microbiology · 2018
Effects of cytochalasin E on Paracoccidioides brasiliensis.
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Mendes G, Baltazar L M, Souza D G, Sá N P, Rosa L H, Rosa C A, Souza-Fagundes E M, Ramos J P, Alves-Silva J, Cota B B, Johann S
Аннотация
AIMS: To determine the effects of cytochalasin E, isolated from the extremophile fungus Aspergillus felis, on the cells of Paracoccidioides brasiliensis Pb18.
METHODS AND RESULTS: Cytochalasin E showed a minimal inhibitory concentration of 3·6 μmol l-1 and minimum fungicidal concentration of 7·2 μmol l-1 on P. brasiliensis by in vitro microdilution and IC50 >964·0 μmol l-1 on murine macrophages. Its selectivity index (>263) indicated that this compound has selectivity for fungal cells. Morphological alterations were determined by optical and fluorescence microscopy, as well as scanning and transmission electron microscopy. Cytochalasin E affected P. brasiliensis bud-forming pseudohyphae, cell morphology, cell walls and cell membranes; caused the release of cellular material; and resulted in the production of reactive oxygen species. In murine macrophages, it affected cytoskeletal actin and inhibited phagocytosis.
CONCLUSION: Cytochalasin E may be useful as an antifungal prototype against P. brasiliensis and in studies on phagocytosis.
SIGNIFICANCE AND IMPACT OF THE STUDY: Paracoccidioides spp. are the etiological agents of paracoccidioidomycosis (PCM). Treatment is prolonged to control the clinical manifestations and prevent relapse. The study on the effects of cytochalasin E in P. brasiliensis is important because it can be used as a prototype for new antifungal drugs and consequently, broadens the treatment options for PCM.
METHODS AND RESULTS: Cytochalasin E showed a minimal inhibitory concentration of 3·6 μmol l-1 and minimum fungicidal concentration of 7·2 μmol l-1 on P. brasiliensis by in vitro microdilution and IC50 >964·0 μmol l-1 on murine macrophages. Its selectivity index (>263) indicated that this compound has selectivity for fungal cells. Morphological alterations were determined by optical and fluorescence microscopy, as well as scanning and transmission electron microscopy. Cytochalasin E affected P. brasiliensis bud-forming pseudohyphae, cell morphology, cell walls and cell membranes; caused the release of cellular material; and resulted in the production of reactive oxygen species. In murine macrophages, it affected cytoskeletal actin and inhibited phagocytosis.
CONCLUSION: Cytochalasin E may be useful as an antifungal prototype against P. brasiliensis and in studies on phagocytosis.
SIGNIFICANCE AND IMPACT OF THE STUDY: Paracoccidioides spp. are the etiological agents of paracoccidioidomycosis (PCM). Treatment is prolonged to control the clinical manifestations and prevent relapse. The study on the effects of cytochalasin E in P. brasiliensis is important because it can be used as a prototype for new antifungal drugs and consequently, broadens the treatment options for PCM.