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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

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.
Total Authors: 11
Document type: Journal article
Web of Science Citations: 6

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: 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: 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: 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 type: Research Grants - Young Investigators Grants
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: 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