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Proteinas de superficie de Paracoccidioides brasiliensis Proteinas de superficie de Paracoccidioides brasiliensis

by Silva Castro, Nadya da

Abstract (Summary)
Paracoccidioides brasiliensis is a temperature dependent dimorphic fungus, theetiological agent of paracoccidioidomycosis. In human, infection starts by inhalation offungal propagules reaching the pulmonary epithelium, where the morphogeneticconversion is correlated with changes in the cell wall composition, organization andstructure. The cell wall constitute an important reservoir of immunoreactive moleculesand potential target for the search of vaccine candidates. In many pathogens, theproteins with glicosilfosfatidilinositol (GPI)-anchors are immunogenic and importantvirulence factors. Thus, P. brasiliensis transcriptome data were analyzed for potentialGPI-anchored proteins localized in plasma membrane or cell wall, as well as forproteins involved in synthesis, attachment and cleavage of the GPI anchor. The proteinswere identified in several functional categories: (i) enzymes: glucanosyltransferases(1-3), (ii) probable surface antigens, (iii) proteins involved in cell wall biosynthesis andstructural role. It was identificated transcript encoding to proteins involved in GPIanchor biosynthesis and hydrolysis. In an effort to elucidate the molecular mechanismsinvolved in the fungus cell wall-assembling and morphogenesis it was performed thestudy of the ?-1,3-glucanosyltransferase 3 (PbGel3). PbGel3 showed one copy ingenome of this fungus with the highest level of transcript and protein in the myceliumphase. The protein was immunolocalized at the surface in both mycelium and yeastphase. The potential role of PbGel3p in cell wall biosynthesis and remodeling wasevidenced by its ability to rescue the phenotype of the Saccharomyces cerevisiae gas1?mutant. The DFG5 (defective in filamentous growth) homologue of P. brasiliensis, aprobably glycosylated and ?-glucan linked cell-wall protein was also studied. Studiesdemonstrated that the recombinant PbDfg5p binds to extracellular matrix components,indicating that it can be important for initial steps leading of P. brasiliensis attachmentand colonization of host tissues. Because of its essential biological role, uniquebiochemistry, structural organization and the absence of the most of their constituents inmammalians cells, the cell wall is an attractive target for the development of newantifungal agents and essential for understanding the fungal pathogenesis. Paracoccidioides brasiliensis is a temperature dependent dimorphic fungus, theetiological agent of paracoccidioidomycosis. In human, infection starts by inhalation offungal propagules reaching the pulmonary epithelium, where the morphogeneticconversion is correlated with changes in the cell wall composition, organization andstructure. The cell wall constitute an important reservoir of immunoreactive moleculesand potential target for the search of vaccine candidates. In many pathogens, theproteins with glicosilfosfatidilinositol (GPI)-anchors are immunogenic and importantvirulence factors. Thus, P. brasiliensis transcriptome data were analyzed for potentialGPI-anchored proteins localized in plasma membrane or cell wall, as well as forproteins involved in synthesis, attachment and cleavage of the GPI anchor. The proteinswere identified in several functional categories: (i) enzymes: glucanosyltransferases(1-3), (ii) probable surface antigens, (iii) proteins involved in cell wall biosynthesis andstructural role. It was identificated transcript encoding to proteins involved in GPIanchor biosynthesis and hydrolysis. In an effort to elucidate the molecular mechanismsinvolved in the fungus cell wall-assembling and morphogenesis it was performed thestudy of the ?-1,3-glucanosyltransferase 3 (PbGel3). PbGel3 showed one copy ingenome of this fungus with the highest level of transcript and protein in the myceliumphase. The protein was immunolocalized at the surface in both mycelium and yeastphase. The potential role of PbGel3p in cell wall biosynthesis and remodeling wasevidenced by its ability to rescue the phenotype of the Saccharomyces cerevisiae gas1?mutant. The DFG5 (defective in filamentous growth) homologue of P. brasiliensis, aprobably glycosylated and ?-glucan linked cell-wall protein was also studied. Studiesdemonstrated that the recombinant PbDfg5p binds to extracellular matrix components,indicating that it can be important for initial steps leading of P. brasiliensis attachmentand colonization of host tissues. Because of its essential biological role, uniquebiochemistry, structural organization and the absence of the most of their constituents inmammalians cells, the cell wall is an attractive target for the development of newantifungal agents and essential for understanding the fungal pathogenesis.
This document abstract is also available in Portuguese.
Bibliographical Information:

Advisor:Bergmann Morais Ribeiro; Célia Maria de Almeida Soares; Augusto Schrank; Ana Amélia Lorenzetti Cavalcante Neto; Ivan Torres Nicolau de Campos

School:Universidade de Brasília

School Location:Brazil

Source Type:Master's Thesis

Keywords:paracoccidioides brasiliensis -1,3-glicanosiltransferas

ISBN:

Date of Publication:05/12/2008

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