Proteomic Profiling of Paracoccidioides brasiliensis in Response to Phenacylideneoxindol Derivative: Unveiling Molecular Targets and Pathways

Background: The treatment of paracoccidioidomycosis (PCM) is a challenge, and the discovery of new antifungal compounds is crucial. The phenacylideneoxindoles exhibited promising antifungal activity against Paracoccidioides spp., but their mode of action remains unknown. Methods: Through proteomic a...

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Published in:Journal of fungi (Basel) 2023-08, Vol.9 (8), p.854
Main Authors: Silva, Lívia do Carmo, Rocha, Olivia Basso, Portis, Igor Godinho, Santos, Thaynara Gonzaga, Freitas e Silva, Kleber Santiago, Santos Filho, Raimundo Francisco dos, Cunha, Silvio, Alonso, Antônio, Soares, Célia Maria de Almeida, Pereira, Maristela
Format: Article
Language:English
Subjects:
Alcohol
antifungal
Antifungal activity
Cell membranes
Ergosterol
Ethanol
Fermentation
Fungi
Mass spectrometry
Metabolism
nitrogen heterocycles
paracoccidioidomycosis
Peptides
phenacylideneoxindol proteomic
Proteins
Proteomics
Quality of life
Reactive oxygen species
Scientific imaging
South American blastomycosis
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Summary:Background: The treatment of paracoccidioidomycosis (PCM) is a challenge, and the discovery of new antifungal compounds is crucial. The phenacylideneoxindoles exhibited promising antifungal activity against Paracoccidioides spp., but their mode of action remains unknown. Methods: Through proteomic analysis, we investigated the effects of (E)-3-(2-oxo-2-phenylethylidene)indolin-2-one on P. brasiliensis. In addition, we investigated the metabolic alterations of P. brasiliensis in response to the compound. Furthermore, the effects of the compound on the membrane, ethanol production, and reactive oxygen species (ROS) production were verified. Results: We identified differentially regulated proteins that revealed significant metabolic reorganization, including an increase in ethanol production, suggesting the activation of alcoholic fermentation and alterations in the rigidity of fungal cell membrane with an increase of the ergosterol content and formation of ROS. Conclusions: These findings enhance our understanding of the mode of action and response of P. brasiliensis to the investigated promising antifungal compound, emphasizing its potential as a candidate for the treatment of PCM.
ISSN:2309-608X
2309-608X
DOI:10.3390/jof9080854