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

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Autor(es): dc.contributorUniversidade Estadual Paulista (Unesp)-
Autor(es): dc.contributorUniversidade de São Paulo (USP)-
Autor(es): dc.contributorUniv Toronto-
Autor(es): dc.contributorRIKEN Ctr Sustainable Resource Sci-
Autor(es): dc.creatorAlves de Paula e Silva, Ana Carolina [UNESP]-
Autor(es): dc.creatorOliveira, Haroldo Cesar de [UNESP]-
Autor(es): dc.creatorScorzoni, Liliana [UNESP]-
Autor(es): dc.creatorMarcos, Caroline Maria [UNESP]-
Autor(es): dc.creatorSantos, Claudia Tavares dos [UNESP]-
Autor(es): dc.creatorFusco-Almeida, Ana Marisa [UNESP]-
Autor(es): dc.creatorGuerta Salina, Ana Carolina [UNESP]-
Autor(es): dc.creatorMedeiros, Alexandra Ivo [UNESP]-
Autor(es): dc.creatorAlmeida, Fausto-
Autor(es): dc.creatorLi, Sheena Claire-
Autor(es): dc.creatorBoone, Charles-
Autor(es): dc.creatorMendes-Giannini, Maria J. S. [UNESP]-
Data de aceite: dc.date.accessioned2022-02-22T00:08:57Z-
Data de disponibilização: dc.date.available2022-02-22T00:08:57Z-
Data de envio: dc.date.issued2020-12-09-
Data de envio: dc.date.issued2020-12-09-
Data de envio: dc.date.issued2019-10-31-
Fonte completa do material: dc.identifierhttp://dx.doi.org/10.1128/AAC.01909-18-
Fonte completa do material: dc.identifierhttp://hdl.handle.net/11449/196268-
Fonte: dc.identifier.urihttp://educapes.capes.gov.br/handle/11449/196268-
Descrição: dc.descriptionThe 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.-
Descrição: dc.descriptionConselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)-
Descrição: dc.descriptionFundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)-
Descrição: dc.descriptionCoordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)-
Descrição: dc.descriptionPrograma de Doutorado Sanduiche no Exterior (PDSE)-
Descrição: dc.descriptionPrograma de Apoio ao Desenvolvimento Cientifico da Faculdade de Ciencias Farmaceuticas da UNESP (PADC/FCF)-
Descrição: dc.descriptionPro-Reitora de Pesquisa da UNESP (PROPe/UNESP)-
Descrição: dc.descriptionUniv Estadual Paulista, Fac Ciencias Farmaceut, Dept Clin Anal, Araraquara, SP, Brazil-
Descrição: dc.descriptionUniv Estadual Paulista, Fac Ciencias Farmaceut, Dept Biol Sci, Araraquara, SP, Brazil-
Descrição: dc.descriptionUniv Sao Paulo, Fac Med Ribeirao Preto, Dept Biochem & Immunol, Ribeirao Preto, SP, Brazil-
Descrição: dc.descriptionUniv Sao Paulo, Fac Med Ribeirao Preto, Dept Cellular Mol Biol & Pathogen Bioagents, Ribeirao Preto, SP, Brazil-
Descrição: dc.descriptionUniv Toronto, Terrence Donnelly Ctr Cellular & Biomol Res, Dept Mol Genet, Toronto, ON, Canada-
Descrição: dc.descriptionRIKEN Ctr Sustainable Resource Sci, Saitama, Japan-
Descrição: dc.descriptionUniv Estadual Paulista, Fac Ciencias Farmaceut, Dept Clin Anal, Araraquara, SP, Brazil-
Descrição: dc.descriptionUniv Estadual Paulista, Fac Ciencias Farmaceut, Dept Biol Sci, Araraquara, SP, Brazil-
Descrição: dc.descriptionCNPq: 403586/2012-7-
Descrição: dc.descriptionFAPESP: 2016/17048-4-
Descrição: dc.descriptionFAPESP: 2015/03700-9-
Descrição: dc.descriptionFAPESP: 2015/14023-8-
Descrição: dc.descriptionFAPESP: 2013/10917-9-
Formato: dc.format13-
Idioma: dc.languageen-
Publicador: dc.publisherAmer Soc Microbiology-
Relação: dc.relationAntimicrobial Agents And Chemotherapy-
???dc.source???: dc.sourceWeb of Science-
Palavras-chave: dc.subjectParacoccidioides lutzii-
Palavras-chave: dc.subjectdecyl gallate-
Palavras-chave: dc.subjectchemical-genetic interaction-
Palavras-chave: dc.subjectN-glycosylation-
Palavras-chave: dc.subjectmechanisms of action-
Título: dc.titleDecyl Gallate as a Possible Inhibitor of N-Glycosylation Process in Paracoccidioides lutzii-
Tipo de arquivo: dc.typelivro digital-
Aparece nas coleções:Repositório Institucional - Unesp

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