In Vitro and In Vivo Effect of Peptides Derived from 14-3-3 Paracoccidioides spp. Protein

Author(s):Show less -

Scorzoni, Liliana ^[1] ; Alves de Paula e Silva, Ana Carolina ^[1] ; de Oliveira, Haroldo Cesar ^[1] ; dos Santos, Claudia Tavares ^[1] ; Singulani, Junya de Lacorte ^[1] ; Assato, Patricia Akemi ^[1] ; Marcos, Caroline Maria ^[1] ; Oliveira, Lariane Teodoro ^[1] ; Fregonezi, Nathalia Ferreira ^[1] ; Pereira Rossi, Diego Conrado ^[2] ; Roque da Silva, Leandro Buffoni ^[2] ; Taborda, Carlos Pelleschi ^[2] ; Fusco-Almeida, Ana Marisa ^[1] ; Soares Mendes-Giannini, Maria Jose ^[1]

Affiliation

^[1] Sao Paulo State Univ UNESP, Sch Pharmaceut Sci, BR-14800903 Sao Paulo - Brazil

^[2] Univ Sao Paulo, Inst Biomed Sci, Dept Microbiol, BR-05508000 Sao Paulo - Brazil

• Document type: Journal article
• Source: JOURNAL OF FUNGI; v. 7, n. 1 JAN 2021.
• Web of Science Citations: 0

Abstract

Background: Paracoccidioidomycosis (PCM) is a chronic disease that causes sequelae and requires prolonged treatment; therefore, new therapeutic approaches are necessary. In view of this, three peptides from Paracoccidioides brasiliensis 14-3-3 protein were selected based on its immunogenicity and therapeutic potential. Methods: The in vitro antifungal activity and cytotoxicity of the 14-3-3 peptides were evaluated. The influence of the peptides in immunological and survival aspects was evaluated in vivo, using Galleria mellonella and the expression of antimicrobial peptide genes in Caenorhabditis elegans. Results: None of the peptides were toxic to HaCaT (skin keratinocyte), MRC-5 (lung fibroblast), and A549 (pneumocyte) cell lines, and only P1 exhibited antifungal activity against Paracoccidioides spp. The peptides could induce an immune response in G. mellonella. Moreover, the peptides caused a delay in the death of Paracoccidioides spp. infected larvae. Regarding C. elegans, the three peptides were able to increase the expression of the antimicrobial peptides. These peptides had essential effects on different aspects of Paracoccidioides spp. infection showing potential for a therapeutic vaccine. Future studies using mammalian methods are necessary to validate our findings. (AU)

• FAPESP's process: 16/08730-6 - Fungal pathogenicity: environmental effects, immune response and vaccine modulation in the Brazilian endemic mycoses paracoccidioidomycosis and histoplasmosis
• Grantee: Carlos Pelleschi Taborda
• Support type: Research Projects - Thematic Grants
• FAPESP's process: 16/17048-4 - Two-component signal transduction (TCST) system as a new target for the treatment of paracoccidioidomycosis
• Grantee: Caroline Maria Marcos
• Support type: Scholarships in Brazil - Post-Doctorate
• FAPESP's process: 15/14023-8 - Use of peptides with anti-adhesive activity in Paracoccidoides spp. in the treatment and prophylaxis of the paracoccidioidomycosis
• Grantee: Haroldo Cesar de Oliveira
• Support type: Scholarships in Brazil - Post-Doctorate
• FAPESP's process: 15/03700-9 - Alternative animal as a model to study Paracoccidioides- host interaction: virulence, efficacy and toxicology of antifungal compounds and new preventive treatments
• Grantee: Maria José Soares Mendes Giannini
• Support type: Regular Research Grants
• FAPESP's process: 13/10917-9 - Alternative animal models: Virulence of different phylogenetic species of Paracoccidioides and effect of the 30kDa 43kDa protein and their antibodies
• Grantee: Liliana Scorzoni
• Support type: Scholarships in Brazil - Post-Doctorate
• FAPESP's process: 14/10446-9 - Evaluation of new therapies and biomarkers in paracoccidioidomycosis: antifungal activity of alkyl gallates in alternative models and mice and identification of circulating microRNAs
• Grantee: Junya de Lacorte Singulani
• Support type: Scholarships in Brazil - Doctorate