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

Detalhes bibliográficos
Autor(a) principal: Gravi, Ellen Tihe [UNIFESP]
Data de Publicação: 2012
Outros Autores: Paschoalin, Thaysa [UNIFESP], Dias, Bianca Rachid [UNIFESP], Moreira, Dayson F., Belizario, Jose Ernesto [UNIFESP], Oliveira, Vitor [UNIFESP], Carmona, Adriana Karaoglanovic [UNIFESP], Juliano, Maria Aparecida [UNIFESP], Travassos, Luiz Rodolpho [UNIFESP], Rodrigues, Elaine Guadelupe [UNIFESP]
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Repositório Institucional da UNIFESP
Texto Completo: http://dx.doi.org/10.3109/13693786.2011.590825
http://repositorio.unifesp.br/handle/11600/34420
Resumo: 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.
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spelling Identification of a metallopeptidase with TOP-like activity in Paracoccidioides brasiliensis, with increased expression in a virulent strainParacoccidioides brasiliensismetallopeptidasethimet oligopeptidasebradykininFRET peptidesParacoccidioidomycosis (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.Universidade Federal de São Paulo Escola Paulista Med UNIFESP EP, Dept Microbiol Imunol & Parasitol, Unidade Oncol Expt UNONEX, BR-04023062 São Paulo, BrazilUniversidade Federal de São Paulo Escola Paulista Med UNIFESP EP, Dept Biofis, BR-04023062 São Paulo, BrazilUniv São Paulo USP, Dept Farmacol, São Paulo, BrazilUniversidade Federal de São Paulo Escola Paulista Med UNIFESP EP, Dept Microbiol Imunol & Parasitol, Unidade Oncol Expt UNONEX, BR-04023062 São Paulo, BrazilUniversidade Federal de São Paulo Escola Paulista Med UNIFESP EP, Dept Biofis, BR-04023062 São Paulo, BrazilWeb of ScienceFundação 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)Informa HealthcareUniversidade Federal de São Paulo (UNIFESP)Universidade de São Paulo (USP)Gravi, Ellen Tihe [UNIFESP]Paschoalin, Thaysa [UNIFESP]Dias, Bianca Rachid [UNIFESP]Moreira, Dayson F.Belizario, Jose Ernesto [UNIFESP]Oliveira, Vitor [UNIFESP]Carmona, Adriana Karaoglanovic [UNIFESP]Juliano, Maria Aparecida [UNIFESP]Travassos, Luiz Rodolpho [UNIFESP]Rodrigues, Elaine Guadelupe [UNIFESP]2016-01-24T14:17:40Z2016-01-24T14:17:40Z2012-01-01info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersion81-90http://dx.doi.org/10.3109/13693786.2011.590825Medical Mycology. London: Informa Healthcare, v. 50, n. 1, p. 81-90, 2012.10.3109/13693786.2011.5908251369-3786http://repositorio.unifesp.br/handle/11600/34420WOS:000298103400011engMedical Mycologyinfo:eu-repo/semantics/openAccesshttp://informahealthcare.com/userimages/ContentEditor/1255620309227/Copyright_And_Permissions.pdfreponame:Repositório Institucional da UNIFESPinstname:Universidade Federal de São Paulo (UNIFESP)instacron:UNIFESP2021-09-29T11:24:45Zoai:repositorio.unifesp.br/:11600/34420Repositório InstitucionalPUBhttp://www.repositorio.unifesp.br/oai/requestbiblioteca.csp@unifesp.bropendoar:34652021-09-29T11:24:45Repositório Institucional da UNIFESP - Universidade Federal de São Paulo (UNIFESP)false
dc.title.none.fl_str_mv Identification of a metallopeptidase with TOP-like activity in Paracoccidioides brasiliensis, with increased expression in a virulent strain
title Identification of a metallopeptidase with TOP-like activity in Paracoccidioides brasiliensis, with increased expression in a virulent strain
spellingShingle Identification of a metallopeptidase with TOP-like activity in Paracoccidioides brasiliensis, with increased expression in a virulent strain
Gravi, Ellen Tihe [UNIFESP]
Paracoccidioides brasiliensis
metallopeptidase
thimet oligopeptidase
bradykinin
FRET peptides
title_short Identification of a metallopeptidase with TOP-like activity in Paracoccidioides brasiliensis, with increased expression in a virulent strain
title_full Identification of a metallopeptidase with TOP-like activity in Paracoccidioides brasiliensis, with increased expression in a virulent strain
title_fullStr Identification of a metallopeptidase with TOP-like activity in Paracoccidioides brasiliensis, with increased expression in a virulent strain
title_full_unstemmed Identification of a metallopeptidase with TOP-like activity in Paracoccidioides brasiliensis, with increased expression in a virulent strain
title_sort Identification of a metallopeptidase with TOP-like activity in Paracoccidioides brasiliensis, with increased expression in a virulent strain
author Gravi, Ellen Tihe [UNIFESP]
author_facet Gravi, Ellen Tihe [UNIFESP]
Paschoalin, Thaysa [UNIFESP]
Dias, Bianca Rachid [UNIFESP]
Moreira, Dayson F.
Belizario, Jose Ernesto [UNIFESP]
Oliveira, Vitor [UNIFESP]
Carmona, Adriana Karaoglanovic [UNIFESP]
Juliano, Maria Aparecida [UNIFESP]
Travassos, Luiz Rodolpho [UNIFESP]
Rodrigues, Elaine Guadelupe [UNIFESP]
author_role author
author2 Paschoalin, Thaysa [UNIFESP]
Dias, Bianca Rachid [UNIFESP]
Moreira, Dayson F.
Belizario, Jose Ernesto [UNIFESP]
Oliveira, Vitor [UNIFESP]
Carmona, Adriana Karaoglanovic [UNIFESP]
Juliano, Maria Aparecida [UNIFESP]
Travassos, Luiz Rodolpho [UNIFESP]
Rodrigues, Elaine Guadelupe [UNIFESP]
author2_role author
author
author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv Universidade Federal de São Paulo (UNIFESP)
Universidade de São Paulo (USP)
dc.contributor.author.fl_str_mv Gravi, Ellen Tihe [UNIFESP]
Paschoalin, Thaysa [UNIFESP]
Dias, Bianca Rachid [UNIFESP]
Moreira, Dayson F.
Belizario, Jose Ernesto [UNIFESP]
Oliveira, Vitor [UNIFESP]
Carmona, Adriana Karaoglanovic [UNIFESP]
Juliano, Maria Aparecida [UNIFESP]
Travassos, Luiz Rodolpho [UNIFESP]
Rodrigues, Elaine Guadelupe [UNIFESP]
dc.subject.por.fl_str_mv Paracoccidioides brasiliensis
metallopeptidase
thimet oligopeptidase
bradykinin
FRET peptides
topic Paracoccidioides brasiliensis
metallopeptidase
thimet oligopeptidase
bradykinin
FRET peptides
description 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.
publishDate 2012
dc.date.none.fl_str_mv 2012-01-01
2016-01-24T14:17:40Z
2016-01-24T14:17:40Z
dc.type.driver.fl_str_mv info:eu-repo/semantics/article
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.uri.fl_str_mv http://dx.doi.org/10.3109/13693786.2011.590825
Medical Mycology. London: Informa Healthcare, v. 50, n. 1, p. 81-90, 2012.
10.3109/13693786.2011.590825
1369-3786
http://repositorio.unifesp.br/handle/11600/34420
WOS:000298103400011
url http://dx.doi.org/10.3109/13693786.2011.590825
http://repositorio.unifesp.br/handle/11600/34420
identifier_str_mv Medical Mycology. London: Informa Healthcare, v. 50, n. 1, p. 81-90, 2012.
10.3109/13693786.2011.590825
1369-3786
WOS:000298103400011
dc.language.iso.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv Medical Mycology
dc.rights.driver.fl_str_mv info:eu-repo/semantics/openAccess
http://informahealthcare.com/userimages/ContentEditor/1255620309227/Copyright_And_Permissions.pdf
eu_rights_str_mv openAccess
rights_invalid_str_mv http://informahealthcare.com/userimages/ContentEditor/1255620309227/Copyright_And_Permissions.pdf
dc.format.none.fl_str_mv 81-90
dc.publisher.none.fl_str_mv Informa Healthcare
publisher.none.fl_str_mv Informa Healthcare
dc.source.none.fl_str_mv reponame:Repositório Institucional da UNIFESP
instname:Universidade Federal de São Paulo (UNIFESP)
instacron:UNIFESP
instname_str Universidade Federal de São Paulo (UNIFESP)
instacron_str UNIFESP
institution UNIFESP
reponame_str Repositório Institucional da UNIFESP
collection Repositório Institucional da UNIFESP
repository.name.fl_str_mv Repositório Institucional da UNIFESP - Universidade Federal de São Paulo (UNIFESP)
repository.mail.fl_str_mv biblioteca.csp@unifesp.br
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