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Mechanisms of Action: Physiological Effects

Argentilactone Molecular Targets in Paracoccidioides brasiliensis Identified by Chemoproteomics

Lívia do Carmo Silva, Sinji Borges Ferreira Tauhata, Lilian Cristiane Baeza, Cecília Maria Alves de Oliveira, Lucília Kato, Clayton Luiz Borges, Célia Maria de Almeida Soares, Maristela Pereira
Lívia do Carmo Silva
Laboratório de Biologia Molecular, Instituto de Ciências Biológicas, Universidade Federal de Goiás, Goiânia, Goiás, Brazil
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Sinji Borges Ferreira Tauhata
Laboratório de Biologia Molecular, Instituto de Ciências Biológicas, Universidade Federal de Goiás, Goiânia, Goiás, Brazil
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Lilian Cristiane Baeza
Laboratório de Biologia Molecular, Instituto de Ciências Biológicas, Universidade Federal de Goiás, Goiânia, Goiás, BrazilCentro de Ciências Médicas e Farmacêuticas, Universidade Estadual do Oeste do Paraná, Cascavel, Paraná, Brazil
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Cecília Maria Alves de Oliveira
Laboratório de Produtos Naturais, Instituto de Química, Universidade Federal de Goiás, Goiânia, Brazil
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Lucília Kato
Laboratório de Produtos Naturais, Instituto de Química, Universidade Federal de Goiás, Goiânia, Brazil
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Clayton Luiz Borges
Laboratório de Biologia Molecular, Instituto de Ciências Biológicas, Universidade Federal de Goiás, Goiânia, Goiás, Brazil
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Célia Maria de Almeida Soares
Laboratório de Biologia Molecular, Instituto de Ciências Biológicas, Universidade Federal de Goiás, Goiânia, Goiás, Brazil
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Maristela Pereira
Laboratório de Biologia Molecular, Instituto de Ciências Biológicas, Universidade Federal de Goiás, Goiânia, Goiás, Brazil
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DOI: 10.1128/AAC.00737-18
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ABSTRACT

Paracoccidioidomycosis (PCM) is the cause of many deaths from systemic mycoses. The etiological agents of PCM belong to the Paracoccidioides genus, which is restricted to Latin America. The infection is acquired through the inhalation of conidia that primarily lodge in the lungs and may disseminate to other organs and tissues. The treatment for PCM is commonly performed via the administration of antifungals such as amphotericin B, co-trimoxazole, and itraconazole. The antifungal toxicity and side effects, in addition to their long treatment times, have stimulated research for new bioactive compounds. Argentilactone is a compound that was isolated from the Brazilian savanna plant Hyptis ovalifolia, and it has been suggested to be a potent antifungal, inhibiting the dimorphism of P. brasiliensis and the enzymatic activity of isocitrate lyase, a key enzyme of the glyoxylate cycle. This work was developed due to the importance of elucidating the putative mode of action of argentilactone. The chemoproteomics approach via affinity chromatography was the methodology used to explore the interactions between P. brasiliensis proteins and argentilactone. A total of 109 proteins were identified and classified functionally. The most representative functional categories were related to amino acid metabolism, energy, and detoxification. Argentilactone inhibited the enzymatic activity of malate dehydrogenase, citrate synthase, and pyruvate dehydrogenase. Furthermore, argentilactone induces the production of reactive oxygen species and inhibits the biosynthesis of cell wall polymers.

FOOTNOTES

    • Received 18 April 2018.
    • Returned for modification 5 July 2018.
    • Accepted 17 August 2018.
    • Accepted manuscript posted online 27 August 2018.
  • Supplemental material for this article may be found at https://doi.org/10.1128/AAC.00737-18.

  • Copyright © 2018 American Society for Microbiology.

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Argentilactone Molecular Targets in Paracoccidioides brasiliensis Identified by Chemoproteomics
Lívia do Carmo Silva, Sinji Borges Ferreira Tauhata, Lilian Cristiane Baeza, Cecília Maria Alves de Oliveira, Lucília Kato, Clayton Luiz Borges, Célia Maria de Almeida Soares, Maristela Pereira
Antimicrobial Agents and Chemotherapy Oct 2018, 62 (11) e00737-18; DOI: 10.1128/AAC.00737-18

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Argentilactone Molecular Targets in Paracoccidioides brasiliensis Identified by Chemoproteomics
Lívia do Carmo Silva, Sinji Borges Ferreira Tauhata, Lilian Cristiane Baeza, Cecília Maria Alves de Oliveira, Lucília Kato, Clayton Luiz Borges, Célia Maria de Almeida Soares, Maristela Pereira
Antimicrobial Agents and Chemotherapy Oct 2018, 62 (11) e00737-18; DOI: 10.1128/AAC.00737-18
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KEYWORDS

Paracoccidioides
antifungal
targets
argentilactone
chemoproteomics
drug discovery

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