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Characterization and evaluation of the role in virulence of the CSP adhesin of Paracoccidioides spp

Grant number: 14/20229-5
Support type:Scholarships in Brazil - Scientific Initiation
Effective date (Start): November 01, 2014
Effective date (End): October 31, 2015
Field of knowledge:Biological Sciences - Microbiology
Principal Investigator:Maria José Soares Mendes Giannini
Grantee:Daniella Sayuri Yamazaki
Home Institution: Faculdade de Ciências Farmacêuticas (FCFAR). Universidade Estadual Paulista (UNESP). Campus de Araraquara. Araraquara , SP, Brazil

Abstract

The Paracoccidioides genus consists of dimorphic fungi, pathogens of paracoccidioidomycosis (PCM). The fungi of this genus have some features that allow their growth under adverse conditions, which may contribute to disease development, and have mechanisms that allow them to adhere to and invade host tissues. The adhesion occurs through of a specific class of cell wall proteins, called adhesins, that are able to mediate the interactions of the fungus with host tissues during infection. Recently, our group performed the cloning and heterologous expression of the CSP protein of P. lutzii that shown to be involved in the virulence of this fungi, and the recombinant protein was able to inhibit about 15% the adhesion of P. lutzii to A549 pneumocytes and furthermore, treatment of the various components of the extracellular matrix with the CSP protein led to a significant inhibition of adhesion of P. lutzii f to the extracellular matrix components: laminin, fibronectin and type I and IV collagen. Since there are few adhesins described for P. lutzii, the study of CSP increases our knowledge about the molecular arsenal used by this specie during its interaction with the host. Therefore, the aim of this work is to investigate the role of this protein in the fungus-host interaction and in order to accomplish that specific antibody will be produced to evaluate the influence of this protein on Paracoccidioides spp in the adhesion process, studying the modifications in the cytoskeleton caused by the treatment with the CSP recombinant protein. Also, the intracellular localization of this protein will be done by microscopic methods as well as the evaluation of the influence of CSP protein in Paracoccidioides spp virulence in vivo, using Galleria mellonella as model.