Decyl Gallate as a Possible Inhibitor of N-Glycosylation Process in Paracoccidioides lutzii .

Autor:	de Paula E Silva ACA; Department of Clinical Analysis, Faculdade de Ciências Farmacêuticas, Universidade Estadual Paulista, Araraquara, São Paulo, Brazil ana_alpasi@hotmail.com gianninimj@gmail.com., de Oliveira HC; Department of Clinical Analysis, Faculdade de Ciências Farmacêuticas, Universidade Estadual Paulista, Araraquara, São Paulo, Brazil., Scorzoni L; Department of Clinical Analysis, Faculdade de Ciências Farmacêuticas, Universidade Estadual Paulista, Araraquara, São Paulo, Brazil., Marcos CM; Department of Clinical Analysis, Faculdade de Ciências Farmacêuticas, Universidade Estadual Paulista, Araraquara, São Paulo, Brazil., Santos CTD; Department of Clinical Analysis, Faculdade de Ciências Farmacêuticas, Universidade Estadual Paulista, Araraquara, São Paulo, Brazil., Fusco-Almeida AM; Department of Clinical Analysis, Faculdade de Ciências Farmacêuticas, Universidade Estadual Paulista, Araraquara, São Paulo, Brazil., Salina ACG; Department of Biological Sciences, Faculdade de Ciências Farmacêuticas, Universidade Estadual Paulista, Araraquara, São Paulo, Brazil.; Department of Biochemistry and Immunology, Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, São Paulo, Brazil., Medeiros AI; Department of Biological Sciences, Faculdade de Ciências Farmacêuticas, Universidade Estadual Paulista, Araraquara, São Paulo, Brazil., Almeida F; Department of Cellular/Molecular Biology and Pathogenic Bioagents, Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, São Paulo, Brazil., Li SC; Department of Molecular Genetics, Terrence Donnelly Centre for Cellular and Biomolecular Research, University of Toronto, Toronto, Ontario, Canada.; RIKEN Center for Sustainable Resource Science, Saitama, Japan., Boone C; Department of Molecular Genetics, Terrence Donnelly Centre for Cellular and Biomolecular Research, University of Toronto, Toronto, Ontario, Canada., Mendes-Giannini MJS; Department of Clinical Analysis, Faculdade de Ciências Farmacêuticas, Universidade Estadual Paulista, Araraquara, São Paulo, Brazil ana_alpasi@hotmail.com gianninimj@gmail.com.
Jazyk:	angličtina
Zdroj:	Antimicrobial agents and chemotherapy [Antimicrob Agents Chemother] 2019 Oct 22; Vol. 63 (11). Date of Electronic Publication: 2019 Oct 22 (Print Publication: 2019).
DOI:	10.1128/AAC.01909-18
Abstrakt:	The available antifungal therapeutic arsenal is limited. The search for alternative drugs with fewer side effects and new targets remains a major challenge. Decyl gallate (G14) is a derivative of gallic acid with a range of biological activities and broad-spectrum antifungal activity. Previously, our group demonstrated the promising anti- Paracoccidioides activity of G14. In this work, to evaluate the antifungal characteristics of G14 for Paracoccidioides lutzii , a chemical-genetic interaction analysis was conducted on a Saccharomyces cerevisiae model. N-glycosylation and/or the unfolded protein response pathway was identified as a high-confidence process for drug target prediction. The overactivation of unfolded protein response (UPR) signaling was confirmed using this model with IRE1/ATF6/PERK genes tagged with green fluorescent protein (GFP). In P. lutzii , this prediction was confirmed by the low activity of glycosylated enzymes [α-(1,3)-glucanase, N -acetyl-β-d-glucosaminidase (NAGase), and α-(1,4)-amylase], by hyperexpression of genes involved with the UPR and glycosylated enzymes, and by the reduction in the amounts of glycosylated proteins and chitin. All of these components are involved in fungal cell wall integrity and are dependent on the N-glycosylation process. This loss of integrity was confirmed by the reduction in mitochondrial activity, impaired budding, enhancement of wall permeability, and a decrease in viability. These events led to a reduction of the ability of fungi to adhere on human lung epithelial cells (A549) in vitro Therefore, G14 may have an important role in balancing the inflammatory reaction caused by fungal infection, without interfering with the microbicidal activity of nitric oxide. This work provides new information on the activity of G14, a potential anti- Paracoccidioides compound. (Copyright © 2019 American Society for Microbiology.)
Databáze:	MEDLINE
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