XI International Meeting on Paracoccidioidomycosis

XI International Meeting on Paracoccidioidomycosis

Resume:10-1

Poster (Painel)

10-1

INFLUENCE OF N-GLYCOSYLATION ON Paracoccidioides brasiliensis MORPHOGENESIS/GROWTH AND IMMUNE RESPONSE OF THE HOST CELLS

Authors:

Fausto Bruno dos Reis Almeida (USP - Universidade de São Paulo) ; Fernanda Caroline de Carvalho (USP - Universidade de São Paulo) ; Vânia Sammartino Mariano (USP - Universidade de São Paulo) ; Ana Claudia Paiva Alegre (USP - Universidade de São Paulo) ; Roberto do Nascimento Silva (USP - Universidade de São Paulo) ; Ebert Seixas Hanna (USP - Universidade de São Paulo) ; Maria Cristina Roque-barreira (USP - Universidade de São Paulo)

Abstract

The fungus Paracoccidioides brasiliensis is a human pathogen that causes the paracoccidioidomycosis, the most prevalent systemic mycosis in Latin America. Here, we report the inhibition of N-linked glycosylation by tunicamycin on yeast cells of P. brasiliensis. In general, N-linked glycans are involved in correct protein folding, intracellular transport and prevention of proteolytic degradation. Cell wall of P. brasiliensis., as well as of many other fungi, is a network of glycoproteins and polysaccharides, such as chitin, featuring several functions. Concerning the fungal cell wall polysaccharides, chitin is among the best studied. It is the second most abundant polysaccharide in nature and abounds in fungal cells wall, consisting of an unbranched homopolymer of 1,4-&beta-linked N-acetyl-D-glucosamine that typically add structural strength to the wall. The chitinolytic enzyme machinery of fungi consists of chitinases and N-acetyl-&beta-D-glucosaminidase (NAGase) that play important roles on the fungal cell wall metabolism. Recently, our group has described a lectin involved on P. brasiliensis growth/morphogenesis process, besides inducing high and persistent production of TNF-&alpha and nitric oxide by macrophages. This lectin is endowed of NAGase activity and is supposed to be accounted for the fungal growth. We have verified herein that N-glycans are embodied on the NAGase activity from P. brasiliensis, consequently N-glycans are required for the adequate growth and morphogenesis of P. brasiliensis yeasts. In addition to the effect in the whole yeast, the induced underglycosylation has inhibited some biological activities of fungal proteins contained in crude cell extract. The results provided by this study demonstrate that N-glycosylation of P. brasiliensis proteins is crucial for many fungal biological processes, as well as for the yeast interaction with host cells.਀ Financial support: FAPESP and FAEPA.

Keyword: N-glycans, Paracoccidioides brasiliensis, N-acetyl-β-D-glucosaminidase

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