Use of peptides with anti-adhesive activity in Paracoccidoides spp. in the treatment and prophylaxis of the paracoccidioidomycosis

• Grant number: 15/14023-8
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• Start date: October 01, 2015
• End date: February 04, 2019
• Field of knowledge: Health Sciences - Pharmacy
• Principal Investigator: Maria José Soares Mendes Giannini
• Grantee: Haroldo Cesar de Oliveira
• Host Institution: Faculdade de Ciências Farmacêuticas (FCFAR). Universidade Estadual Paulista (UNESP). Campus de Araraquara. Araraquara , SP, Brazil
• Associated scholarship(s): 16/20631-3 - The host immune response to anti-adhesive peptides treatment and morphological changes during infection of pathogenic fungi, BE.EP.PD

Abstract

The fungi of the Paracoccidioides genus are dimorphic fungi, etiological agents of paracoccidioidomycosis (PCM), systemic mycosis of great interest in Latin America and Brazil. The antifungal arsenal available for PCM treatment is limited and most agents have high toxicity. The search for new agents that innovate the mechanism of action are of outmost importance and urgency for the treatment of PCM as well as for the treatment of other systemic mycoses. In innovative terms, difficult the adhesion of the fungus to host cells can be an efficient way in helping to combat the infection, once unable to adhere, the fungus will be unable to colonize different host tissues, the nutrients acquiring will be difficult, facilitating the host immune system to combat the infection. In this sense, the candidate for post-doctoral scholarship during his PhD study, due to the importance of the adhesion in the infection process of Paracoccidioides spp., using Phage Display, was able to identify four peptides that bind with high affinity to Paracoccidioides spp. cell wall, with ability to inhibit adhesion of the fungus to the host structures in vitro, reduce the virulence of the fungus and, in addition, modulate the host immune system generating a more effective response in resolving the infection and these results show the importance of invest in the characterization of these peptides for use in the treatment and prophylaxis of PCM. Because of these characteristics, this project aims to use murine model to establish which kind of response that immunizations with these peptides can cause to the host, what course will the infection take in mice treated with the peptides and what the effects of immunization with the peptides followed by the known treatment of the disease. The project also aims to better characterize these peptides, defining the targets to which they bind in the fungus cell wall as well as increasing the scope of use of these peptides in other fungal species of medical importance as Histoplasma capsulatum, Cryptococcus neoformans and Candida albicans evaluating aspects such as influence on virulence and biofilm formation.

Scientific publications

(17)

(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)

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)

SINGULANI, JUNYA L.; SCORZONI, LILIANA; DE OLIVEIRA, HAROLDO C.; MARCOS, CAROLINE M.; ASSATO, PATRICIA A.; FUSCO-ALMEIDA, ANA MARISA; MENDES-GIANNINI, MARIA JOSE S.. Applications of Invertebrate Animal Models to Dimorphic Fungal Infections. JOURNAL OF FUNGI, v. 4, n. 4, DEC 2018. (17/06658-9, 16/17048-4, 15/14023-8)

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)

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)

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)

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)

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)

SELEGATO, DENISE MEDEIROS; FREIRE, RAFAEL TEIXEIRA; PILON, ALAN CESAR; BIASETTO, CAROLINA RABAL; DE OLIVEIRA, HAROLDO CESAR; DE ABREU, LUCAS MAGALHAES; ARAUJO, ANGELA REGINA; BOLZANI, VANDERLAN DA SILVA; CASTRO-GAMBOA, IAN. Improvement of bioactive metabolite production in microbial cultures-A systems approach by OSMAC and deconvolution-based (HNMR)-H-1 quantification. Magnetic Resonance in Chemistry, v. 57, n. 8, p. 458-471, AUG 2019. (16/13292-8, 13/07600-3, 15/14023-8, 14/05935-0, 09/54083-9)

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)

FREGONEZI, NATHALIA FERREIRA; OLIVEIRA, LARIANE TEODORO; SINGULANI, JUNYA DE LACORTE; MARCOS, CAROLINE MARIA; DOS SANTOS, CLAUDIA TAVARES; TAYLOR, MARIA LUCIA; MENDES-GIANNINI, MARIA JOSE SOARES; DE OLIVEIRA, HAROLDO CESAR; FUSCO-ALMEIDA, ANA MARISA. Heat Shock Protein 60, Insights to Its Importance in Histoplasma capsulatum: From Biofilm Formation to Host-Interaction. FRONTIERS IN CELLULAR AND INFECTION MICROBIOLOGY, v. 10, JAN 22 2021. (18/15877-9, 15/14023-8, 16/11836-0, 17/06658-9, 16/17048-4)

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)

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)

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)

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; et al. 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. (11/18038-9, 15/14023-8, 16/17048-4)