Proteomic identification of metabolic changes in Paracoccidioides brasiliensis induced by a nitroheteroarylchalcone

Author:

Júnior Marcos ABC1ORCID,Silva Lívia C1ORCID,Rocha Olivia B1ORCID,Oliveira Amanda A1,Portis Igor G1ORCID,Alonso Antonio2ORCID,Alonso Lais2,Silva Kleber SF1,Gomes Marcelo N34,Andrade Carolina H5ORCID,Soares Célia MA1ORCID,Pereira Maristela1ORCID

Affiliation:

1. Laboratory of Molecular Biology, Institute of Biological Sciences, Federal University of Goiás, Goiânia, Goiás, Brazil

2. Institute of Physics, Federal University of Goiás, Goiânia, Goiás, Brazil

3. InsiChem, Goiás State University, Anápolis, Goiás, Brazil

4. Faculdade Metropolitana de Anápolis, Anápolis, Goiás, Brazil

5. Laboratory for Molecular Modeling & Drug Design, Faculty of Pharmacy, Federal University of Goiás, Goiânia, Goiás, Brazil

Abstract

Aim: To access the metabolic changes caused by a chalcone derivative (LabMol-75) through a proteomic approach. Methods: Proteomic analysis was performed after 9 h of Paracoccidioides brasiliensis yeast ( Pb18) cell incubation with the LabMol-75 at MIC. The proteomic findings were validated through in vitro and in silico assays. Results: Exposure to the compound led to the downregulation of proteins associated with glycolysis and gluconeogenesis, β-oxidation, the citrate cycle and the electron transport chain. Conclusion: LabMol-75 caused an energetic imbalance in the fungus metabolism and deep oxidative stress. Additionally, the in silico molecular docking approach pointed to this molecule as a putative competitive inhibitor of DHPS.

Funder

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior

Instituto Nacional de Ciência e Tecnologia de Estratégias de Interação Patógeno-Hospedeiro

Conselho Nacional de Desenvolvimento Científico e Tecnológico

Financiadora de Estudos e Projetos

Programa de Apoio a Núcleos de Excelência

Ministério da Ciência e Tecnologia

Fundo Nacional de Desenvolvimento Científico e Tecnológico

Publisher

Future Medicine Ltd

Subject

Microbiology (medical),Microbiology

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