The Human Pathogen Paracoccidioides brasiliensis Has a Unique 1-Cys Peroxiredoxin That Localizes Both Intracellularly and at the Cell Surface
Paracoccidioides brasiliensis is a temperature-dependent dimorphic fungus that causes systemic paracoccidioidomycosis, a granulomatous disease. The massive production of reactive oxygen species (ROS) by the host's cellular immune response is an essential strategy to restrain the fungal growth....
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| Format: | Article |
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Frontiers Media S.A.
2020-08-01
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| Series: | Frontiers in Cellular and Infection Microbiology |
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| Online Access: | https://www.frontiersin.org/article/10.3389/fcimb.2020.00394/full |
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| author | Larissa Valle Guilhen Longo Carlos Alexandre Breyer Gabriela Machado Novaes Gregory Gegembauer Natanael Pinheiro Leitão Carla Elizabete Octaviano Marcos Hikari Toyama Marcos Antonio de Oliveira Rosana Puccia |
| author_facet | Larissa Valle Guilhen Longo Carlos Alexandre Breyer Gabriela Machado Novaes Gregory Gegembauer Natanael Pinheiro Leitão Carla Elizabete Octaviano Marcos Hikari Toyama Marcos Antonio de Oliveira Rosana Puccia |
| author_sort | Larissa Valle Guilhen Longo |
| collection | DOAJ |
| description | Paracoccidioides brasiliensis is a temperature-dependent dimorphic fungus that causes systemic paracoccidioidomycosis, a granulomatous disease. The massive production of reactive oxygen species (ROS) by the host's cellular immune response is an essential strategy to restrain the fungal growth. Among the ROS, the hydroperoxides are very toxic antimicrobial compounds and fungal peroxidases are part of the pathogen neutralizing antioxidant arsenal against the host's defense. Among them, the peroxiredoxins are highlighted, since some estimates suggest that they are capable of decomposing most of the hydroperoxides generated in the host's mitochondria and cytosol. We presently characterized a unique P. brasiliensis 1-Cys peroxiredoxin (PbPrx1). Our results reveal that it can decompose hydrogen peroxide and organic hydroperoxides very efficiently. We showed that dithiolic, but not monothiolic compounds or heterologous thioredoxin reductant systems, were able to retain the enzyme activity. Structural analysis revealed that PbPrx1 has an α/β structure that is similar to the 1-Cys secondary structures described to date and that the quaternary conformation is represented by a dimer, independently of the redox state. We investigated the PbPrx1 localization using confocal microscopy, fluorescence-activated cell sorter, and immunoblot, and the results suggested that it localizes both in the cytoplasm and at the cell wall of the yeast and mycelial forms of P. brasiliensis, as well as in the yeast mitochondria. Our present results point to a possible role of this unique P. brasiliensis 1-Cys Prx1 in the fungal antioxidant defense mechanisms. |
| first_indexed | 2024-12-24T03:14:30Z |
| format | Article |
| id | doaj.art-ec42907d15ab44dbb5f6cafa9721e5af |
| institution | Directory Open Access Journal |
| issn | 2235-2988 |
| language | English |
| last_indexed | 2024-12-24T03:14:30Z |
| publishDate | 2020-08-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Cellular and Infection Microbiology |
| spelling | doaj.art-ec42907d15ab44dbb5f6cafa9721e5af2022-12-21T17:17:41ZengFrontiers Media S.A.Frontiers in Cellular and Infection Microbiology2235-29882020-08-011010.3389/fcimb.2020.00394555396The Human Pathogen Paracoccidioides brasiliensis Has a Unique 1-Cys Peroxiredoxin That Localizes Both Intracellularly and at the Cell SurfaceLarissa Valle Guilhen Longo0Carlos Alexandre Breyer1Gabriela Machado Novaes2Gregory Gegembauer3Natanael Pinheiro Leitão4Carla Elizabete Octaviano5Marcos Hikari Toyama6Marcos Antonio de Oliveira7Rosana Puccia8Departamento de Microbiologia, Imunologia e Parasitologia, Escola Paulista de Medicina—Universidade Federal de São Paulo, São Paulo, BrazilInstituto de Biociências, Universidade Estadual Paulista Júlio de Mesquita Filho, São Paulo, BrazilInstituto de Biociências, Universidade Estadual Paulista Júlio de Mesquita Filho, São Paulo, BrazilDepartamento de Microbiologia, Imunologia e Parasitologia, Escola Paulista de Medicina—Universidade Federal de São Paulo, São Paulo, BrazilDepartamento de Microbiologia, Imunologia e Parasitologia, Escola Paulista de Medicina—Universidade Federal de São Paulo, São Paulo, BrazilDepartamento de Microbiologia, Imunologia e Parasitologia, Escola Paulista de Medicina—Universidade Federal de São Paulo, São Paulo, BrazilInstituto de Biociências, Universidade Estadual Paulista Júlio de Mesquita Filho, São Paulo, BrazilInstituto de Biociências, Universidade Estadual Paulista Júlio de Mesquita Filho, São Paulo, BrazilDepartamento de Microbiologia, Imunologia e Parasitologia, Escola Paulista de Medicina—Universidade Federal de São Paulo, São Paulo, BrazilParacoccidioides brasiliensis is a temperature-dependent dimorphic fungus that causes systemic paracoccidioidomycosis, a granulomatous disease. The massive production of reactive oxygen species (ROS) by the host's cellular immune response is an essential strategy to restrain the fungal growth. Among the ROS, the hydroperoxides are very toxic antimicrobial compounds and fungal peroxidases are part of the pathogen neutralizing antioxidant arsenal against the host's defense. Among them, the peroxiredoxins are highlighted, since some estimates suggest that they are capable of decomposing most of the hydroperoxides generated in the host's mitochondria and cytosol. We presently characterized a unique P. brasiliensis 1-Cys peroxiredoxin (PbPrx1). Our results reveal that it can decompose hydrogen peroxide and organic hydroperoxides very efficiently. We showed that dithiolic, but not monothiolic compounds or heterologous thioredoxin reductant systems, were able to retain the enzyme activity. Structural analysis revealed that PbPrx1 has an α/β structure that is similar to the 1-Cys secondary structures described to date and that the quaternary conformation is represented by a dimer, independently of the redox state. We investigated the PbPrx1 localization using confocal microscopy, fluorescence-activated cell sorter, and immunoblot, and the results suggested that it localizes both in the cytoplasm and at the cell wall of the yeast and mycelial forms of P. brasiliensis, as well as in the yeast mitochondria. Our present results point to a possible role of this unique P. brasiliensis 1-Cys Prx1 in the fungal antioxidant defense mechanisms.https://www.frontiersin.org/article/10.3389/fcimb.2020.00394/fullParacoccidioides brasiliensis1-Cys Prxhydroperoxidesperoxiredoxindimorphic fungiROS |
| spellingShingle | Larissa Valle Guilhen Longo Carlos Alexandre Breyer Gabriela Machado Novaes Gregory Gegembauer Natanael Pinheiro Leitão Carla Elizabete Octaviano Marcos Hikari Toyama Marcos Antonio de Oliveira Rosana Puccia The Human Pathogen Paracoccidioides brasiliensis Has a Unique 1-Cys Peroxiredoxin That Localizes Both Intracellularly and at the Cell Surface Frontiers in Cellular and Infection Microbiology Paracoccidioides brasiliensis 1-Cys Prx hydroperoxides peroxiredoxin dimorphic fungi ROS |
| title | The Human Pathogen Paracoccidioides brasiliensis Has a Unique 1-Cys Peroxiredoxin That Localizes Both Intracellularly and at the Cell Surface |
| title_full | The Human Pathogen Paracoccidioides brasiliensis Has a Unique 1-Cys Peroxiredoxin That Localizes Both Intracellularly and at the Cell Surface |
| title_fullStr | The Human Pathogen Paracoccidioides brasiliensis Has a Unique 1-Cys Peroxiredoxin That Localizes Both Intracellularly and at the Cell Surface |
| title_full_unstemmed | The Human Pathogen Paracoccidioides brasiliensis Has a Unique 1-Cys Peroxiredoxin That Localizes Both Intracellularly and at the Cell Surface |
| title_short | The Human Pathogen Paracoccidioides brasiliensis Has a Unique 1-Cys Peroxiredoxin That Localizes Both Intracellularly and at the Cell Surface |
| title_sort | human pathogen paracoccidioides brasiliensis has a unique 1 cys peroxiredoxin that localizes both intracellularly and at the cell surface |
| topic | Paracoccidioides brasiliensis 1-Cys Prx hydroperoxides peroxiredoxin dimorphic fungi ROS |
| url | https://www.frontiersin.org/article/10.3389/fcimb.2020.00394/full |
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