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 Opportunities: Regular Research Grants
• Duration: July 01, 2015 - December 31, 2017
• Field of knowledge: Biological Sciences - Microbiology - Applied Microbiology
• Principal Investigator: Maria José Soares Mendes Giannini
• Grantee: Maria José Soares Mendes Giannini
• Host Institution: Faculdade de Ciências Farmacêuticas (FCFAR). Universidade Estadual Paulista (UNESP). Campus de Araraquara. Araraquara , SP, Brazil
• Associated 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

(20)

(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)

MARCOS, CAROLINE MARIA; DE OLIVEIRA, HAROLDO CESAR; ASSATO, PATRICIA AKEMI; CASTELLI, RAFAEL FERNANDO; FUSCO-ALMEIDA, ANA MARISA; MENDES-GIANNINI, MARIA JOSE SOARES. Drk1, a Dimorphism Histidine Kinase, Contributes to Morphology, Virulence, and Stress Adaptation in Paracoccidioides brasiliensis. JOURNAL OF FUNGI, v. 7, n. 10, OCT 2021. (16/17048-4, 15/14023-8, 15/03700-9)

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. (15/03700-9, 13/10917-9, 16/17048-4, 15/14023-8)

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; et al. Decyl Gallate as a Possible Inhibitor of N-Glycosylation Process in Paracoccidioides lutzii. Antimicrobial Agents and Chemotherapy, v. 63, n. 11, NOV 2019. (16/17048-4, 15/14023-8, 15/03700-9, 13/10917-9)

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. (14/10446-9, 15/03700-9, 13/10917-9, 15/14023-8)

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; et al. 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. (15/03700-9, 15/14023-8)

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. (14/10446-9, 15/03700-9, 13/10917-9)

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. (15/03700-9)

MARCOS, CAROLINE MARIA; DE OLIVEIRA, HAROLDO CESAR; ASSATO, PATRICIA AKEMI; DE ANDRADE, CLEVERTON ROBERTO; FUSCO-ALMEIDA, ANA MARISA; SOARES MENDES-GIANNINI, MARIA JOSE. Paracoccidioides brasiliensis 14-3-3 protein is important for virulence in a murine model. Medical Mycology, v. 57, n. 7, p. 900-904, OCT 2019. (16/17048-4, 15/14023-8, 15/03700-9)

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; et al. 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. (13/10917-9, 14/10446-9, 15/03700-9)

MARCOS, CAROLINE MARIA; TAMER, GABRIELLE; DE OLIVEIRA, HAROLDO CESAR; ASSATO, PATRICIA AKEMI; SCORZONI, LILIANA; SANTOS, CLAUDIA TAVARES; SINGULANI, JUNYA DE LACORTE; DA SILVA, JULHIANY DE FATIMA; DE ALMEIDA, RODRIGO; ALVES DE PAULA E SILVA, ANA CAROLINA; et al. Down-regulation of TUFM impairs host cell interaction and virulence by Paracoccidioides brasiliensis. SCIENTIFIC REPORTS, v. 9, NOV 20 2019. (13/10917-9, 16/17048-4, 15/14023-8, 15/03700-9, 14/10446-9)

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. (15/03700-9, 13/10917-9)

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; et al. 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. (15/03700-9, 11/18038-9)

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. (15/14023-8, 14/10446-9, 15/03700-9, 16/17048-4, 13/10917-9)

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.; et al. Fungal Biofilms and Polymicrobial Diseases. JOURNAL OF FUNGI, v. 3, n. 2, JUN 2017. (15/03700-9, 15/14023-8, 13/10917-9, 16/11836-0)

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. (15/03700-9, 13/10917-9)

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. (15/03700-9, 13/10917-9, 15/14023-8)

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.; et al. 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. (08/54806-8, 15/14023-8, 15/03700-9, 16/17048-4, 13/10917-9)

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; et al. 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. (14/10446-9, 15/03700-9, 13/10917-9, 15/14023-8)

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. (13/10917-9, 14/10446-9, 15/03700-9)

SCORZONI, LILIANA; ALVES DE PAULA E SILVA, ANA CAROLINA; DE OLIVEIRA, HAROLDO CESAR; DOS SANTOS, CLAUDIA TAVARES; SINGULANI, JUNYA DE LACORTE; ASSATO, PATRICIA AKEMI; MARCOS, CAROLINE MARIA; OLIVEIRA, LARIANE TEODORO; FREGONEZI, NATHALIA FERREIRA; PEREIRA ROSSI, DIEGO CONRADO; et al. In Vitro and In Vivo Effect of Peptides Derived from 14-3-3 Paracoccidioides spp. Protein. JOURNAL OF FUNGI, v. 7, n. 1, JAN 2021. (16/08730-6, 16/17048-4, 15/14023-8, 15/03700-9, 13/10917-9, 14/10446-9)