Identification of a metallopeptidase with TOP-like activity in Paracoccidioides brasiliensis, with increased expression in a virulent strain

Identification of a metallopeptidase with TOP-like activity in Paracoccidioides brasiliensis, with increased expression in a virulent strain

Author Gravi, Ellen Tihe Autor UNIFESP Google Scholar
Paschoalin, Thaysa Autor UNIFESP Google Scholar
Dias, Bianca Rachid Autor UNIFESP Google Scholar
Moreira, Dayson F. Google Scholar
Belizario, Jose Ernesto Autor UNIFESP Google Scholar
Oliveira, Vitor Autor UNIFESP Google Scholar
Carmona, Adriana Karaoglanovic Autor UNIFESP Google Scholar
Juliano, Maria Aparecida Autor UNIFESP Google Scholar
Travassos, Luiz Rodolpho Autor UNIFESP Google Scholar
Rodrigues, Elaine Guadelupe Autor UNIFESP Google Scholar
Institution Universidade Federal de São Paulo (UNIFESP)
Universidade de São Paulo (USP)
Abstract Paracoccidioidomycosis (PCM), caused by the pathogenic fungus Paracoccidioides brasiliensis, is a systemic mycosis with severe acute and chronic forms. the pathology of PCM is not completely understood, and the role of proteases in the infection is not clearly defined. in this report, we describe a metallopeptidase activity in P. brasiliensis total and cytosolic protein extracts similar to that of mammalian thimet oligopeptidase (TOP). the analogous enzyme was suggested by analysis of P. brasiliensis genome data-bank and by hydrolytic activity of the FRET peptide Abz-GFSPFRQ-EDDnp which was completely inhibited by o-phenanthrolin and significantly inhibited by the TOP inhibitor, JA-2. This activity was also partially inhibited by IgG purified from patients with PCM, but not from normal individuals. As shown by high-performance liquid chromatography (HPLC), the hydrolysis of bradykinin had the same pattern as that of mammalian TOP, and anti-mammalian TOP antibodies significantly inhibited fungal cytosolic peptidase activity. Moreover, anti-mammalian TOP antibodies recognized a component of 80 kDa on fungal cytosol. A P. brasiliensis virulent isolate showed higher gene expression and TOP-like peptidase activity than a non-virulent strain. the release of enzyme following fungal lysis would be consistent with host antibody production and may have a role in the pathogenesis, inflammation and further development of the mycosis.
Keywords Paracoccidioides brasiliensis
thimet oligopeptidase
FRET peptides
Language English
Sponsor Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)
Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)
Date 2012-01-01
Published in Medical Mycology. London: Informa Healthcare, v. 50, n. 1, p. 81-90, 2012.
ISSN 1369-3786 (Sherpa/Romeo, impact factor)
Publisher Informa Healthcare
Extent 81-90
Access rights Open access Open Access
Type Article
Web of Science ID WOS:000298103400011

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