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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

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

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Alves de Paula e Silva, Ana Carolina [1] ; de Oliveira, Haroldo Cesar [1] ; Scorzoni, Liliana [1] ; Marcos, Caroline Maria [1] ; dos Santos, Claudia Tavares [1] ; Fusco-Almeida, Ana Marisa [1] ; Guerta Salina, Ana Carolina [2, 3] ; Medeiros, Alexandra Ivo [3] ; Almeida, Fausto [4] ; Li, Sheena Claire [5, 6] ; Boone, Charles [5] ; Mendes-Giannini, Maria J. S. [1]
Total Authors: 12
Affiliation:
[1] Univ Estadual Paulista, Fac Ciencias Farmaceut, Dept Clin Anal, Araraquara, SP - Brazil
[2] Univ Sao Paulo, Fac Med Ribeirao Preto, Dept Biochem & Immunol, Ribeirao Preto, SP - Brazil
[3] Univ Estadual Paulista, Fac Ciencias Farmaceut, Dept Biol Sci, Araraquara, SP - Brazil
[4] Univ Sao Paulo, Fac Med Ribeirao Preto, Dept Cellular Mol Biol & Pathogen Bioagents, Ribeirao Preto, SP - Brazil
[5] Univ Toronto, Terrence Donnelly Ctr Cellular & Biomol Res, Dept Mol Genet, Toronto, ON - Canada
[6] RIKEN Ctr Sustainable Resource Sci, Saitama - Japan
Total Affiliations: 6
Document type: Journal article
Source: Antimicrobial Agents and Chemotherapy; v. 63, n. 11 NOV 2019.
Web of Science Citations: 0
Abstract

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 {[}alpha-(1,3)-glucanase, N-acetyl-alpha-D-glucosaminidase (NAGase), and alpha-(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. (AU)

FAPESP's process: 16/17048-4 - Two-component signal transduction (TCST) system as a new target for the treatment of paracoccidioidomycosis
Grantee:Caroline Maria Marcos
Support type: Scholarships in Brazil - Post-Doctorate
FAPESP's process: 15/14023-8 - Use of peptides with anti-adhesive activity in Paracoccidoides spp. in the treatment and prophylaxis of the paracoccidioidomycosis
Grantee:Haroldo Cesar de Oliveira
Support type: Scholarships in Brazil - Post-Doctorate
FAPESP's process: 15/03700-9 - Alternative animal as a model to study Paracoccidioides- host interaction: virulence, efficacy and toxicology of antifungal compounds and new preventive treatments
Grantee:Maria José Soares Mendes Giannini
Support type: Regular Research Grants
FAPESP's process: 13/10917-9 - Alternative animal models: Virulence of different phylogenetic species of Paracoccidioides and effect of the 30kDa 43kDa protein and their antibodies
Grantee:Liliana Scorzoni
Support type: Scholarships in Brazil - Post-Doctorate