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Alternative animal as a model to study Paracoccidioides- host interaction: virulence, efficacy and toxicology of antifungal compounds and new preventive treatments

Grant number: 15/03700-9
Support type:Regular Research Grants
Duration: July 01, 2015 - December 31, 2017
Field of knowledge:Biological Sciences - Microbiology
Principal Investigator:Maria José Soares Mendes Giannini
Grantee:Maria José Soares Mendes Giannini
Home Institution: Faculdade de Ciências Farmacêuticas (FCFAR). Universidade Estadual Paulista (UNESP). Campus de Araraquara. Araraquara , SP, Brazil
Assoc. researchers:Ana Marisa Fusco Almeida

Abstract

The paracoccidioidomycosis (PCM) is a fungal infection caused by fungi of the genus Paracoccidioides spp, endemic in South and Central Americas and south of Mexico. This mycosis has increased clinical importance, due to the intensification of its frequency, the severity of their anatomic and clinical forms and the mortality. The PCM is caused by thermo dimorphic fungi which are in mycelial form or yeast, respectively, in nature and in the host. Paracoccidioides genus comprises two species, P. brasiliensis, and P. lutzii, the first of which can be divided into three phylogenetic species denominated S1 S2, PS3. The adaptation to environmental conditions is very important to Paracoccidioides survival during human host infection. The adaptability of some conditions is a vital attribute during its pathogenesis. The use of mammals for scientific research has always been a matter of concern and ethical requirements and good laboratory practices are increasing. Galleria mellonella and C. elegans have been used to study the virulence of microorganisms, antifungal effectiveness; moreover, the evolutionary conservation between the immune system of mammals and invertebrates is an additional factor that supports their use. Due to its importance in host cell invasion, adhesins are intensively investigated by also constitute potential target for therapeutic intervention (drugs and / or vaccines). In this study, we intend to evaluate the process of virulence and host-fungus interaction of two species of Paracoccidioides employing models of invertebrates, likewise the response to treatment by conventional and new antifungal substances will be evaluated. Additionally, in the C. elegans model we will investigate the routes of immune activation triggered by Paracoccidioides, the gp43 protein and 30 kDa (14-3-3) and immunogenic peptides derived beyond from 30 kDa. (AU)

Scientific publications (16)
(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)
ALVES DE PAULA E SILVA, ANA CAROLINA; DE OLIVEIRA, HAROLDO CESAR; SCORZONI, LILIANA; MARCOS, CAROLINE MARIA; DOS SANTOS, CLAUDIA TAVARES; FUSCO-ALMEIDA, ANA MARISA; GUERTA SALINA, ANA CAROLINA; MEDEIROS, ALEXANDRA IVO; ALMEIDA, FAUSTO; LI, SHEENA CLAIRE; BOONE, CHARLES; MENDES-GIANNINI, MARIA J. S. Decyl Gallate as a Possible Inhibitor of N-Glycosylation Process in Paracoccidioides lutzii. Antimicrobial Agents and Chemotherapy, v. 63, n. 11 NOV 2019. Web of Science Citations: 0.
SINGULANI, JUNYA DE LACORTE; SCORZONI, LILIANA; STROHMAYER LOURENCETTI, NATALIA MANUELA; OLIVEIRA, LUANA ROSSI; CONCOARO, ROSANA SILVA; DA SILVA, PATRICIA BENTO; NAZARE, ANA CAROLINA; POLAQUINI, CARLOS ROBERTO; VICTORELLI, FRANCESCA DAMIANI; CHORILLI, MARLUS; REGASINI, LUIS OCTAVIO; FUSCO ALMEIDA, ANA MARISA; SOARES MENDES GIANNINI, MARIA JOSE. Potential of the association of dodecyl gallate with nanostructured lipid system as a treatment for paracoccidioidomycosis: In vitro and in vivo efficacy and toxicity. International Journal of Pharmaceutics, v. 547, n. 1-2, p. 630-636, AUG 25 2018. Web of Science Citations: 1.
SCORZONI, LILIANA; ALVES DE PAULA E SILVA, ANA CAROLINA; DE OLIVEIRA, HAROLDO CESAR; MARCOS, CAROLINE MARIA; SINGULANI, JUNYA DE LACORTE; FUSCO-ALMEIDA, ANA MARISA; SOARES MENDES-GIANNINI, MARIA JOSE. Can passage in Galleria mellonella activate virulence factors of Paracoccidioides brasiliensis as in the murine model?. Medical Mycology, v. 56, n. 3, p. 374-377, APR 2018. Web of Science Citations: 2.
SCORZONI, LILIANA; PILAR DE LUCAS, MARIA; SINGULANI, JUNYA DE LACORTE; DE OLIVEIRA, HAROLDO CESAR; ASSATO, PATRICIA AKEMI; FUSCO-ALMEIDA, ANA MARISA; SOARES MENDES-GIANNINI, MARIA JOSE. Evaluation of &ITCaenorhabditis elegans&IT as a host model for &ITParacoccidioides brasiliensis &ITand &ITParacoccidioides lutzii&IT. PATHOGENS AND DISEASE, v. 76, n. 1 FEB 2018. Web of Science Citations: 1.
SINGULANI, JUNYA DE LACORTE; SCORZONI, LILIANA; GOMES, PAULO CESAR; NAZARE, ANA CAROLINA; POLAQUINI, CARLOS ROBERTO; REGASINI, LUIS OCTAVIO; FUSCO-ALMEIDA, ANA MARISA; SOARES MENDES-GIANNINI, MARIA JOSE. Activity of gallic acid and its ester derivatives in Caenorhabditis elegans and zebrafish (Danio rerio) models. Future Medicinal Chemistry, v. 9, n. 16, p. 1863-1872, OCT 2017. Web of Science Citations: 3.
COSTA-ORLANDI, CAROLINE B.; SARDI, JANAINA C. O.; PITANGUI, NAYLA S.; DE OLIVEIRA, HAROLDO C.; SCORZONI, LILIANA; GALEANE, MARIANA C.; MEDINA-ALARCON, KAILA P.; MELO, WANESSA C. M. A.; MARCELINO, MONICA Y.; BRAZ, JAQUELINE D.; FUSCO-ALMEIDA, ANA MARISA; MENDES-GIANNINI, MARIA JOSE S. Fungal Biofilms and Polymicrobial Diseases. JOURNAL OF FUNGI, v. 3, n. 2 JUN 2017. Web of Science Citations: 16.
SCORZONI, LILIANA; DE PAULA E SILVA, ANA C. A.; MARCOS, CAROLINE M.; ASSATO, PATRICIA A.; DE MELO, WANESSA C. M. A.; DE OLIVEIRA, HAROLDO C.; COSTA-ORLANDI, CAROLINE B.; MENDES-GIANNINI, MARIA J. S.; FUSCO-ALMEIDA, ANA M. Antifungal Therapy: New Advances in the Understanding and Treatment of Mycosis. FRONTIERS IN MICROBIOLOGY, v. 8, JAN 23 2017. Web of Science Citations: 48.
DE OLIVEIRA, HAROLDO C.; MICHALOSKI, JUSSARA S.; DA SILVA, JULHIANY F.; SCORZONI, LILIANA; DE PAULA E SILVA, ANA C. A.; MARCOS, CAROLINE M.; ASSATO, PATRICIA A.; YAMAZAKI, DANIELLE S.; FUSCO-ALMEIDA, ANA M.; GIORDANO, RICARDO J.; MENDES-GIANNINI, MARIA J. S. Peptides Derived from a Phage Display Library Inhibit Adhesion and Protect the Host against Infection by Paracoccidioides brasiliensis and Paracoccidioides lutzii. FRONTIERS IN PHARMACOLOGY, v. 7, DEC 23 2016. Web of Science Citations: 6.
MARCOS, CAROLINE M.; DE OLIVEIRA, HAROLDO C.; ANTUNES DE MELO, WANESSA DE CASSIA M.; DA SILVA, JULHIANY DE FATIMA; ASSATO, PATRICIA A.; SCORZONI, LILIANA; ROSSI, SUELEN A.; DE PAULA E SILVA, ANA C. A.; MENDES-GIANNINI, MARIA J. S.; FUSCO-ALMEIDA, ANA M. Anti-Immune Strategies of Pathogenic Fungi. FRONTIERS IN CELLULAR AND INFECTION MICROBIOLOGY, v. 6, NOV 15 2016. Web of Science Citations: 16.
MARCOS, CAROLINE MARIA; DE OLIVEIRA, HAROLDO CESAR; DA SILVA, JULHIANY DE FATIMA; ASSATO, PATRICIA AKEMI; YAMAZAKI, DANIELLA SAYURI; MORAES DA SILVA, ROSANGELA APARECIDA; SANTOS, CLAUDIA TAVARES; SANTOS-FILHO, NORIVAL ALVES; PORTUONDO, DEIVYS LEANDRO; SOARES MENDES-GIANNINI, MARIA JOSE; FUSCO-ALMEIDA, ANA MARISA. Identification and characterisation of elongation factor Tu, a novel protein involved in Paracoccidioides brasiliensis-host interaction. FEMS Yeast Research, v. 16, n. 7 NOV 2016. Web of Science Citations: 1.
SANGALLI-LEITE, FERNANDA; SCORZONI, LILIANA; ALVES DE PAULA E SILVA, ANA CAROLINA; DA SILVA, JULHIANY DE FATIMA; DE OLIVEIRA, HAROLDO CESAR; SINGULANI, JUNYA DE LACORTE; GULLO, FERNANDA PATRICIA; DA SILVA, ROSANGELA MORAES; REGASINI, LUIS OCTAVIO; SIQUEIRA DA SILVA, DULCE HELENA; BOLZANI, VANDERLAN DA SILVA; FUSCO-ALMEIDA, ANA MARISA; SOARES MENDES-GIANNINI, MARIA JOSE. Synergistic effect of pedalitin and amphotericin B against Cryptococcus neoformans by in vitro and in vivo evaluation. INTERNATIONAL JOURNAL OF ANTIMICROBIAL AGENTS, v. 48, n. 5, p. 504-511, NOV 2016. Web of Science Citations: 12.
SINGULANI, JUNYA DE LACORTE; SCORZONI, LILIANA; ALVES DE PAULA E SILVA, ANA CAROLINA; FUSCO-ALMEIDA, ANA MARISA; SOARES MENDES-GIANNINI, MARIA JOSE. Evaluation of the efficacy of antifungal drugs against Paracoccidioides brasiliensis and Paracoccidioides lutzii in a Galleria mellonella model. INTERNATIONAL JOURNAL OF ANTIMICROBIAL AGENTS, v. 48, n. 3, p. 292-297, SEP 2016. Web of Science Citations: 12.
SCORZONI, LILIANA; SANGALLI-LEITE, FERNANDA; SINGULANI, JUNYA DE LACORTE; ALVES DE PAULA E SILVA, ANA CAROLINA; COSTA-ORLANDI, CAROLINE BARCELOS; FUSCO-ALMEIDA, ANA MARISA; MENDES-GIANNINI, MARIA JOSE SOARES. Searching new antifungals: The use of in vitro and in vivo methods for evaluation of natural compounds. Journal of Microbiological Methods, v. 123, p. 68-78, APR 2016. Web of Science Citations: 17.
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.
DE OLIVEIRA, HAROLDO C.; ASSATO, PATRCIA A.; MARCOS, CAROLINE M.; SCORZONI, LILIANA; SILVA, ANA C. A. DE PAULA E.; DA SILVA, JULHIANY DE FATIMA; SINGULANI, JUNYA DE LACORTE; ALARCON, KAILA M.; FUSCO-ALMEIDA, ANA M.; MENDES-GIANNINI, MARIA J. S. Paracoccidioides-host Interaction: An Overview on Recent Advances in the Paracoccidioidomycosis. FRONTIERS IN MICROBIOLOGY, v. 6, NOV 25 2015. Web of Science Citations: 30.
SCORZONI, LILIANA; ALVES DE PAULA E SILVA, ANA CAROLINA; SINGULANI, JUNYA DE LACORTE; LEITE, FERNANDA SANGALLI; DE OLIVEIRA, HAROLDO CESAR; MORAES DA SILVA, ROSANGELA APARECIDA; FUSCO-ALMEIDA, ANA MARISA; SOARES MENDES-GIANNINI, MARIA JOSE. Comparison of virulence between Paracoccidioides brasiliensis and Paracoccidioides lutzii using Galleria mellonella as a host model. VIRULENCE, v. 6, n. 8, p. 766-776, NOV 17 2015. Web of Science Citations: 15.

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