Effects of cytochalasin E on Paracoccidioides brasiliensis

  • J Appl Microbiol. 2018 Nov;125(5):1296-1307. doi: 10.1111/jam.14053.
G Mendes  1  2 ,  L M Baltazar  1 ,  D G Souza  1 ,  N P Sá  1 ,  L H Rosa  1 ,  C A Rosa  1 ,  E M Souza-Fagundes  3 ,  J P Ramos  3 ,  J Alves-Silva  4 ,  B B Cota  2 ,  S Johann  1
Affiliations
  • 1. Departamento de Microbiologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil.
  • 2. Laboratório de Química de Produtos Naturais Bioativos, Instituto René Rachou, Fundação Oswaldo Cruz, Belo Horizonte, Brazil.
  • 3. Departamento de Fisiologia e Biofísica, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil.
  • 4. Departamento de Morfologia da Universidade Federal de Minas Gerais, Belo Horizonte, Brazil.
PMID: 30053334 DOI: 10.1111/jam.14053
Abstract

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.

Keywords
Paracoccidioides brasiliensis; antifungal activity; cell membrane; cell wall; cytochalasin E; reactive oxygen species.
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