Effects of cytochalasin E on Paracoccidioides brasiliensis

J Appl Microbiol. 2018 Nov;125(5):1296-1307. doi: 10.1111/jam.14053. Epub 2018 Sep 19.

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.

MeSH terms

  • Antifungal Agents / isolation & purification
  • Antifungal Agents / pharmacology*
  • Aspergillus / chemistry
  • Cytochalasins / isolation & purification
  • Cytochalasins / pharmacology*
  • Microbial Sensitivity Tests
  • Paracoccidioides / drug effects*

Substances

  • Antifungal Agents
  • Cytochalasins
  • cytochalasin E