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Characterization and functional analysis of the gene for 14-3-3 protein involved in the process of adhesion of Paracoccidioides sp. complex and identification of potential targets in the treatment of paracoccidioidomycosis

Abstract

Paracoccidioidomycosis is a mycosis caused by Paracoccidioides sp complex. The successful colonization of host tissues by the fungus is a complex event, usually involving a ligand encoded by the pathogen (adhesins) and a cell receptor. In a recent study a protein of 30 kDa of P. brasiliensis has isolated, ligand laminin and characterized as belong to the family 14-3-3. These proteins may participate in processes of apoptosis, signal transduction, cell cycle regulation and transcription in a manner not yet determined. Saccharomyces cerevisiae possesses two isoforms of 14-3-3 protein: Bmh1 Bmh2, encoded by the genes BMH1 BMH2, respectively, which have 92% identity with each other and when compared with the amino acid sequence of 14-3-3 of P. brasiliensis, the isoform Bmh1 of S. cerevisisae revealed an identity of 76% and Bmh2 isoform of 80%. Thus, this project aims to use the model S. cerevisiae to study functionally the 14-3-3 protein of P. brasiliensis and P.lutzii. Additionally, in order to investigate the potential of this adhesin as a target for the design of therapeutic approaches, monoclonal antibody will be produced from recombinant molecules in order to verify the localization of this system in cells infected with P. brasiliensis and P. lutzii as well as, in S. cerevisiae complemented with the gene of 14-3-3 of P. brasiliensis (functional homologue). On the other hand, the study will be conducted related to the structure and antifungal activity of gallic acid-derived molecules in S. cerevisiae (homologous functional), and in the Paracoccidioides sp. complex to check the interference of gallic acid in the adhesion process and direct potential targets associated with this interaction. (AU)

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Scientific publications (6)
(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)
BERNARDI, THAIS; DA SILVA, JULHIANY DE FATIMA; VICENTIN, JULIANA; DE OLIVEIRA, HAROLDO CESAR; ASSATO, PATRICIA AKEMI; MARCOS, CAROLINE MARIA; ALVES DE PAULA E SILVA, ANA CAROLINA; MORAES DA SILVA, ROSANGELA APARECIDA; REGASINI, LUIS OCTAVIO; SIQUEIRA SILVA, DULCE HELENA; BOLZANI, VANDERLAN DA SILVA; FUSCO-ALMEIDA, ANA MARISA; SOARES MENDES-GIANNINI, MARIA JOSE. Anti-apoptotic effects of decyl gallate on the induction of apoptosis in A549 pneumocytes by Paracoccidioides brasiliensis gp43. Medical Mycology, v. 55, n. 8, p. 890-894, NOV 2017. Web of Science Citations: 1.
MARIA MARCOS, CAROLINE; DE FATIMA DA SILVA, JULHIANY; CESAR DE OLIVEIRA, HAROLDO; AKEMI ASSATO, PATRICIA; DE LACORTE SINGULANI, JUNYA; MARIA LOPEZ, ANGELA; PATRICIA TAMAYO, DIANA; HERNANDEZ-RUIZ, ORVILLE; MCEWEN, JUAN G.; SOARES MENDES-GIANNINI, MARIA JOSE; MARISA FUSCO-ALMEIDA, ANA. Decreased expression of 14-3-3 in Paracoccidioides brasiliensis confirms its involvement in fungal pathogenesis. VIRULENCE, v. 7, n. 2, p. 72-84, FEB 17 2016. Web of Science Citations: 9.
ASSATO, PATRICIA AKEMI; DA SILVA, JULHIANY DE FATIMA; DE OLIVEIRA, HAROLDO CESAR; MARCOS, CAROLINE MARIA; ROSSI, DANUZA; VALENTINI, SANDRO ROBERTO; SOARES MENDES-GIANNINI, MARIA JOSE; ZANELLI, CLESLEI FERNANDO; FUSCO-ALMEIDA, ANA MARISA. Functional analysis of Paracoccidioides brasiliensis 14-3-3 adhesin expressed in Saccharomyces cerevisiae. BMC Microbiology, v. 15, NOV 4 2015. Web of Science Citations: 6.
DE OLIVEIRA, HAROLDO C.; DA SILVA, JULHIANY DE FATIMA; SCORZONI, LILIANA; MARCOS, CAROLINE M.; ROSSI, SUEEN A.; DE PAULA E SILVA, ANA C. A.; ASSATO, PATRICIA A.; DA SILVA, ROSANGELA A. M.; FUSCO-ALMEIDA, ANA M.; MENDES-GIANNINI, MARIA J. S. Importance of adhesins in virulence of Paracoccidioides spp.. FRONTIERS IN MICROBIOLOGY, v. 6, APR 10 2015. Web of Science Citations: 20.
DE OLIVEIRA, HAROLDO CESAR; DA SILVA, JULHIANY DE FATIMA; MATSUMOTO, MARCELO TERUYUKI; MARCOS, CAROLINE MARIA; DA SILVA, ROBERTA PERES; MORAES DA SILVA, ROSANGELA APARECIDA; VENEZIANO LABATE, MONICA TERESA; LABATE, CARLOS ALBERTO; FUSCO ALMEIDA, ANA MARISA; SOARES MENDES GIANNINI, MARIA JOSE. Alterations of protein expression in conditions of copper-deprivation for Paracoccidioides lutzii in the presence of extracellular matrix components. BMC Microbiology, v. 14, DEC 13 2014. Web of Science Citations: 6.
DA SILVA, JULHIANY DE FATIMA; DE OLIVEIRA, HAROLDO CESAR; MARCOS, CAROLINE MARIA; MORAES DA SILVA, ROSANGELA APARECIDA; DA COSTA, TANIA ALVES; GARCIA CALICH, VERA LUCIA; FUSCO ALMEIDA, ANA MARISA; SOARES MENDES-GIANNINI, MARIA JOSE. Paracoccidoides brasiliensis 30 kDa Adhesin: Identification as a 14-3-3 Protein, Cloning and Subcellular Localization in Infection Models. PLoS One, v. 8, n. 4 APR 30 2013. Web of Science Citations: 13.

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