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Argentilactone Molecular Targets in Paracoccidioides brasiliensis Identified by Chemoproteomics.
Antimicrob Agents Chemother. 2018 11; 62(11)AA

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.

Authors+Show Affiliations

Laboratório de Biologia Molecular, Instituto de Ciências Biológicas, Universidade Federal de Goiás, Goiânia, Goiás, Brazil.Laboratório de Biologia Molecular, Instituto de Ciências Biológicas, Universidade Federal de Goiás, Goiânia, Goiás, Brazil.Laboratório de Biologia Molecular, Instituto de Ciências Biológicas, Universidade Federal de Goiás, Goiânia, Goiás, Brazil. Centro de Ciências Médicas e Farmacêuticas, Universidade Estadual do Oeste do Paraná, Cascavel, Paraná, Brazil.Laboratório de Produtos Naturais, Instituto de Química, Universidade Federal de Goiás, Goiânia, Brazil.Laboratório de Produtos Naturais, Instituto de Química, Universidade Federal de Goiás, Goiânia, Brazil.Laboratório de Biologia Molecular, Instituto de Ciências Biológicas, Universidade Federal de Goiás, Goiânia, Goiás, Brazil.Laboratório de Biologia Molecular, Instituto de Ciências Biológicas, Universidade Federal de Goiás, Goiânia, Goiás, Brazil.Laboratório de Biologia Molecular, Instituto de Ciências Biológicas, Universidade Federal de Goiás, Goiânia, Goiás, Brazil maristelaufg@gmail.com.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

30150478

Citation

Silva, Lívia do Carmo, et al. "Argentilactone Molecular Targets in Paracoccidioides Brasiliensis Identified By Chemoproteomics." Antimicrobial Agents and Chemotherapy, vol. 62, no. 11, 2018.
Silva LDC, Tauhata SBF, Baeza LC, et al. Argentilactone Molecular Targets in Paracoccidioides brasiliensis Identified by Chemoproteomics. Antimicrob Agents Chemother. 2018;62(11).
Silva, L. D. C., Tauhata, S. B. F., Baeza, L. C., de Oliveira, C. M. A., Kato, L., Borges, C. L., de Almeida Soares, C. M., & Pereira, M. (2018). Argentilactone Molecular Targets in Paracoccidioides brasiliensis Identified by Chemoproteomics. Antimicrobial Agents and Chemotherapy, 62(11). https://doi.org/10.1128/AAC.00737-18
Silva LDC, et al. Argentilactone Molecular Targets in Paracoccidioides Brasiliensis Identified By Chemoproteomics. Antimicrob Agents Chemother. 2018;62(11) PubMed PMID: 30150478.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Argentilactone Molecular Targets in Paracoccidioides brasiliensis Identified by Chemoproteomics. AU - Silva,Lívia do Carmo, AU - Tauhata,Sinji Borges Ferreira, AU - Baeza,Lilian Cristiane, AU - de Oliveira,Cecília Maria Alves, AU - Kato,Lucília, AU - Borges,Clayton Luiz, AU - de Almeida Soares,Célia Maria, AU - Pereira,Maristela, Y1 - 2018/10/24/ PY - 2018/04/18/received PY - 2018/08/17/accepted PY - 2018/8/29/pubmed PY - 2019/10/11/medline PY - 2018/8/29/entrez KW - Paracoccidioides KW - antifungal KW - argentilactone KW - chemoproteomics KW - drug discovery KW - targets JF - Antimicrobial agents and chemotherapy JO - Antimicrob. Agents Chemother. VL - 62 IS - 11 N2 - 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. SN - 1098-6596 UR - https://www.unboundmedicine.com/medline/citation/30150478/Argentilactone_Molecular_Targets_in_Paracoccidioides_brasiliensis_Identified_by_Chemoproteomics_ L2 - http://aac.asm.org/cgi/pmidlookup?view=long&pmid=30150478 DB - PRIME DP - Unbound Medicine ER -