XI International Meeting on Paracoccidioidomycosis

XI International Meeting on Paracoccidioidomycosis

Resume:6-1

Poster (Painel)

6-1	*PROTEIN PBPGA1 OF Paracoccidoides brasiliensis* INTERACTS WITH EXTRACELLULAR MATRIX COMPONENTS AND INDUCES THE RELEASE OF TNF-α AND NITRIC OXIDE BY MURINE MACROPHAGES਀**
Authors:	Clarissa Xavier Resende Valim (FMRP-USP - Faculdade de Medicina de Ribeirão Preto) ; Fausto Bruno dos Reis Almeida (FMRP-USP - Faculdade de Medicina de Ribeirão Preto) ; Paulo Sergio Rodrigues Coelho (FMRP-USP - Faculdade de Medicina de Ribeirão Preto) ; Maria Célia Jamur (FMRP-USP - Faculdade de Medicina de Ribeirão Preto)

Abstract

The termo-dimorphic fungi Paracoccidioides brasiliensis is the etiologic agent of paracoccidioidomycosis (PCM), one of the most prevalent mycosis in Latin America. P. brasiliensis cell wall components interact with host cells and can influence the pathogenesis of PCM. In P. brasiliensis and other fungi, most proteins that compose the cell wall are GPI anchored proteins. These proteins are involved in cell-cell adhesion and cell-tissue adhesion, with a key role in the interaction between fungal cells and host cells. Protein PbPga1 is a GPI protein of P. brasiliensis and has unknown function. PbPga1 is located on the yeast cell wall as a ring at the neck between the mother cell and the bud and apically in cells transitioning to mycelium form. Protein PbPga1 is up-regulated in the pathogenic yeast form. In this study, we examined the capacity of a recombinant protein PbPga1, produced in Pichia pastoris and purified in a NI-NTA column, to bind to extracellular matrix components and to murine macrophages. The identity of the recombinant PbPga1 was confirmed by mass spectrometry. The recombinant PbPga1 was able to bind to laminin, fibronectin, collagen I and collagen IV in a dose-dependent manner. Interestingly, the recombinant PgPga1 induced mouse peritoneal macrophages to release high levels of TNF-α in vitro. Recombinant PgPga1 also induced the production of high levels of nitric oxide (NO) in these cells. These results suggest that PbPga1 can facilitate the adhesion of P. brasiliensis in host tissues which is a crucial step in pathogenic process and a prerequisite for host colonization. Furthermore, high levels of NO have been associated with suppression of cell immunity. Taken together the results indicate that PbPga1 may play an important role on the PCM pathogenesis.

Keyword: Interação fungo-hospedeiro, Macrófagos murinos, MEC, Paracoccidioides brasilensis, Proteina GPI

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