Peptides Derived from a Phage Display Library Inhibit Adhesion and Protect the Host against Infection by Paracoccidioides brasiliensis and Paracoccidioides lutzii

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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.

• Document type: Journal article
• Source: FRONTIERS IN PHARMACOLOGY; v. 7, DEC 23 2016.
• Web of Science Citations: 6

Abstract

Paracoccidioides brasiliensis and Paracoccidioides lutzii are dimorphic fungi and are the etiological agents of paracoccidioidomycosis (PCM). Adhesion is one of the most important steps in infections with Paracoccidioides and is responsible for the differences in the virulence of isolates of these fungi. Because of the importance of adhesion to the establishment of an infection, this study focused on the preliminary development of a new therapeutic strategy to inhibit adhesion by Paracoccidioides, thus inhibiting infection and preventing the disease. We used two phage display libraries to select peptides that strongly bind to the Paracoccidioides cell wall to inhibit adhesion to host cells and extracellular matrix (ECM) components (laminin, fibronectin, and type I and type IV collagen). This approach allowed us to identify four peptides that inhibited up to 64% of the adhesion of Paracoccidioides to pneumocytes in vitro and inhibited the adhesion to the ECM components by up to 57%. Encouraged by these results, we evaluated the ability of these peptides to protect Galleria mellonella from Paracoccidioides infection by treating G. mellonella larvae with the different peptides prior to infection with Paracoccidioides and observing larval survival. The results show that all of the peptides tested increased the survival of the larvae infected with P brasiliensis by up to 64% and by up to 60% in those infected with P lutzii. These data may open new horizons for therapeutic strategies to prevent PCM, and anti-adhesion therapy could be an important strategy. (AU)

• FAPESP's process: 08/54806-8 - Identification of new molecular markers in angiogenic retina and rational design of new therapeutic agents for eye diseases with a vascular component
• Grantee: Ricardo Jose Giordano
• Support Opportunities: Research Grants - Young Investigators Grants
• 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 Opportunities: Scholarships in Brazil - Post-Doctoral
• 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 Opportunities: Regular Research 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 Opportunities: Scholarships in Brazil - Post-Doctoral
• 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 Opportunities: Scholarships in Brazil - Post-Doctoral