title: Peptides Derived from a Phage Display Library Inhibit Adhesion and Protect the Host against Infection byParacoccidioides brasiliensisandParacoccidioides lutzii.
abstract: Paracoccidioides brasiliensisandParacoccidioides lutziiare dimorphic fungi and are the etiological agents of paracoccidioidomycosis (PCM). Adhesion is one of the most important steps in infections withParacoccidioides 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 byParacoccidioides, thus inhibiting infection and preventing the disease. We used two phage display libraries to select peptides that strongly bind to theParacoccidioidescell 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 ofParacoccidioidesto pneumocytesin vitroand inhibited the adhesion to the ECM components by up to 57%. Encouraged by these results, we evaluated the ability of these peptides to protectGalleria mellonellafromParacoccidioidesinfection by treatingG. mellonellalarvae with the different peptides prior to infection withParacoccidioidesand observing larval survival. The results show that all of the peptides tested increased the survival of the larvae infected withP. brasiliensisby up to 64% and by up to 60% in those infected withP. lutzii. These data may open new horizons for therapeutic strategies to prevent PCM, and anti-adhesion therapy could be an important strategy.
authors.affiliation: Universidade Estadual Paulista (UNESP), Faculdade de Ciências Farmacêuticas, Câmpus Araraquara, São Paulo Brasil.
authors.forename: Haroldo C
authors.initials: HC
authors.lastname: de Oliveira
authors.affiliation: Universidade de São Paulo (USP), Instituto de Química, Câmpus São Paulo, São Paulo Brasil.
authors.forename: Jussara S
authors.initials: JS
authors.lastname: Michaloski
authors.affiliation: Universidade Estadual Paulista (UNESP), Faculdade de Ciências Farmacêuticas, Câmpus Araraquara, São Paulo Brasil.
authors.forename: Julhiany F
authors.initials: JF
authors.lastname: da Silva
authors.affiliation: Universidade Estadual Paulista (UNESP), Faculdade de Ciências Farmacêuticas, Câmpus Araraquara, São Paulo Brasil.
authors.forename: Liliana
authors.initials: L
authors.lastname: Scorzoni
authors.affiliation: Universidade Estadual Paulista (UNESP), Faculdade de Ciências Farmacêuticas, Câmpus Araraquara, São Paulo Brasil.
authors.forename: Ana C A
authors.initials: AC
authors.lastname: de Paula E Silva
authors.affiliation: Universidade Estadual Paulista (UNESP), Faculdade de Ciências Farmacêuticas, Câmpus Araraquara, São Paulo Brasil.
authors.forename: Caroline M
authors.initials: CM
authors.lastname: Marcos
authors.affiliation: Universidade Estadual Paulista (UNESP), Faculdade de Ciências Farmacêuticas, Câmpus Araraquara, São Paulo Brasil.
authors.forename: Patrícia A
authors.initials: PA
authors.lastname: Assato
authors.affiliation: Universidade Estadual Paulista (UNESP), Faculdade de Ciências Farmacêuticas, Câmpus Araraquara, São Paulo Brasil.
authors.forename: Daniella S
authors.initials: DS
authors.lastname: Yamazaki
authors.affiliation: Universidade Estadual Paulista (UNESP), Faculdade de Ciências Farmacêuticas, Câmpus Araraquara, São Paulo Brasil.
authors.forename: Ana M
authors.initials: AM
authors.lastname: Fusco-Almeida
authors.affiliation: Universidade de São Paulo (USP), Instituto de Química, Câmpus São Paulo, São Paulo Brasil.
authors.forename: Ricardo J
authors.initials: RJ
authors.lastname: Giordano
authors.affiliation: Universidade Estadual Paulista (UNESP), Faculdade de Ciências Farmacêuticas, Câmpus Araraquara, São Paulo Brasil.
authors.forename: Maria J S
authors.initials: MJ
authors.lastname: Mendes-Giannini
keywords: Paracoccidioides spp.; adhesion; anti-adhesive peptides; paracoccidioidomycosis; phage display