Exposure of Paracoccidioides brasiliensis to Mebendazole Leads to Inhibition of Fungal Energy Production

• Published in: Antibiotics (Basel) Vol. 12; no. 2; p. 206
• Main Authors: Rocha, Olivia Basso, E Silva, Kleber Santiago Freitas, Moraes, Dayane, Borges, Clayton Luiz, Soares, Célia Maria de Almeida, Pereira, Maristela
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 18.01.2023; MDPI
• Subjects: Adenosine triphosphate; ATP; Cell cycle; Cytochrome; Cytochrome-c oxidase; Cytochromes; Dehydrogenases; Disease; Drugs; Electron transport; Electron transport chain; Energy; Energy metabolism; Enzymes; Ethanol; Exposure; Fermentation; Fungal diseases; Fungal infections; Fungi; Fungicides; Glycolysis; Mebendazole; Metabolism; Microscopy; Mitochondria; Oxidative stress; paracoccidioidomycosis; Pathogens; Proteins; Proteomics; repositioning; South American blastomycosis; Superoxide dismutase; paracoccidioidomycosis; proteomics; repositioning
• ISSN: 2079-6382; 2079-6382
• DOI: 10.3390/antibiotics12020206

Paracoccidioidomycosis (PCM) is a fungal disease caused by organisms of the genus spp. The treatment of the disease is lengthy and includes several adverse effects. Various methodologies focus on the search for new treatments against fungal disease, including the repositioning of drugs. Our group showed the fungicidal effect of mebendazole in cells. Thus, understanding the effect of exposing fungal cells to mebendazole is significant for further studies in order to demonstrate it as a potential drug for the treatment of PCM. A proteomic analysis of exposed to mebendazole was carried out. Analyses showed that exposure strongly affected the pathways related to energy production, such as glycolysis, fermentation, and the electron transport chain. The quantification of adenosine triphosphate (ATP) and mitochondrial activity demonstrated that the drug alters the electron chain, resulting in an increase in oxidative stress. Enzymes such as superoxide dismutase (SOD) and cytochrome c oxidase (Cyt C) were repressed in cells exposed to mebendazole. The concentration of ethanol produced by the cells under treatment demonstrated that the attempt to produce energy through fermentation is also arrested. Thus, the drug inhibits fungal growth through changes in energy metabolism, making it a promising compound for use in the treatment of PCM.