Analyses of the three 1-Cys Peroxiredoxins from Aspergillus fumigatus reveal that cytosolic Prx1 is central to H2O2 metabolism and virulence

Abstract Standing among the front defense strategies against pathogens, host phagocytic cells release various oxidants. Therefore, pathogens have to cope with stressful conditions at the site of infection. Peroxiredoxins (Prx) are highly reactive and abundant peroxidases that can support virulence a...

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Autores principales:	Marina Campos Rocha, Krissia Franco de Godoy, Renata Bannitz-Fernandes, João H. T. Marilhano Fabri, Mayra M. Ferrari Barbosa, Patrícia Alves de Castro, Fausto Almeida, Gustavo Henrique Goldman, Anderson Ferreira da Cunha, Luis E. S. Netto, Marcos Antonio de Oliveira, Iran Malavazi
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2018
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/76476fbdb8c84c26bedd08eff953e9a9
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spelling	oai:doaj.org-article:76476fbdb8c84c26bedd08eff953e9a92021-12-02T15:07:45ZAnalyses of the three 1-Cys Peroxiredoxins from Aspergillus fumigatus reveal that cytosolic Prx1 is central to H2O2 metabolism and virulence10.1038/s41598-018-30108-22045-2322https://doaj.org/article/76476fbdb8c84c26bedd08eff953e9a92018-08-01T00:00:00Zhttps://doi.org/10.1038/s41598-018-30108-2https://doaj.org/toc/2045-2322Abstract Standing among the front defense strategies against pathogens, host phagocytic cells release various oxidants. Therefore, pathogens have to cope with stressful conditions at the site of infection. Peroxiredoxins (Prx) are highly reactive and abundant peroxidases that can support virulence and persistence of pathogens in distinct hosts. Here, we revealed that the opportunistic human pathogen A. fumigatus presents three 1-Cys Prx (Prx6 subfamily), which is unprecedented. We showed that PrxB and PrxC were in mitochondria, while Prx1 was in cytosol. As observed for other Prxs, recombinant Prx1 and PrxC decomposed H2O2 at elevated velocities (rate constants in the 107 M−1s−1 range). Deletion mutants for each Prx displayed higher sensitivity to oxidative challenge in comparison with the wild-type strain. Additionally, cytosolic Prx1 was important for A. fumigatus survival upon electron transport dysfunction. Expression of Prxs was dependent on the SakAHOG1 MAP kinase and the Yap1YAP1 transcription factor, a global regulator of the oxidative stress response in fungi. Finally, cytosolic Prx1 played a major role in pathogenicity, since it is required for full virulence, using a neutropenic mouse infection model. Our data indicate that the three 1-Cys Prxs act together to maintain the redox balance of A. fumigatus.Marina Campos RochaKrissia Franco de GodoyRenata Bannitz-FernandesJoão H. T. Marilhano FabriMayra M. Ferrari BarbosaPatrícia Alves de CastroFausto AlmeidaGustavo Henrique GoldmanAnderson Ferreira da CunhaLuis E. S. NettoMarcos Antonio de OliveiraIran MalavaziNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 8, Iss 1, Pp 1-18 (2018)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Marina Campos Rocha Krissia Franco de Godoy Renata Bannitz-Fernandes João H. T. Marilhano Fabri Mayra M. Ferrari Barbosa Patrícia Alves de Castro Fausto Almeida Gustavo Henrique Goldman Anderson Ferreira da Cunha Luis E. S. Netto Marcos Antonio de Oliveira Iran Malavazi Analyses of the three 1-Cys Peroxiredoxins from Aspergillus fumigatus reveal that cytosolic Prx1 is central to H2O2 metabolism and virulence
description	Abstract Standing among the front defense strategies against pathogens, host phagocytic cells release various oxidants. Therefore, pathogens have to cope with stressful conditions at the site of infection. Peroxiredoxins (Prx) are highly reactive and abundant peroxidases that can support virulence and persistence of pathogens in distinct hosts. Here, we revealed that the opportunistic human pathogen A. fumigatus presents three 1-Cys Prx (Prx6 subfamily), which is unprecedented. We showed that PrxB and PrxC were in mitochondria, while Prx1 was in cytosol. As observed for other Prxs, recombinant Prx1 and PrxC decomposed H2O2 at elevated velocities (rate constants in the 107 M−1s−1 range). Deletion mutants for each Prx displayed higher sensitivity to oxidative challenge in comparison with the wild-type strain. Additionally, cytosolic Prx1 was important for A. fumigatus survival upon electron transport dysfunction. Expression of Prxs was dependent on the SakAHOG1 MAP kinase and the Yap1YAP1 transcription factor, a global regulator of the oxidative stress response in fungi. Finally, cytosolic Prx1 played a major role in pathogenicity, since it is required for full virulence, using a neutropenic mouse infection model. Our data indicate that the three 1-Cys Prxs act together to maintain the redox balance of A. fumigatus.
format	article
author	Marina Campos Rocha Krissia Franco de Godoy Renata Bannitz-Fernandes João H. T. Marilhano Fabri Mayra M. Ferrari Barbosa Patrícia Alves de Castro Fausto Almeida Gustavo Henrique Goldman Anderson Ferreira da Cunha Luis E. S. Netto Marcos Antonio de Oliveira Iran Malavazi
author_facet	Marina Campos Rocha Krissia Franco de Godoy Renata Bannitz-Fernandes João H. T. Marilhano Fabri Mayra M. Ferrari Barbosa Patrícia Alves de Castro Fausto Almeida Gustavo Henrique Goldman Anderson Ferreira da Cunha Luis E. S. Netto Marcos Antonio de Oliveira Iran Malavazi
author_sort	Marina Campos Rocha
title	Analyses of the three 1-Cys Peroxiredoxins from Aspergillus fumigatus reveal that cytosolic Prx1 is central to H2O2 metabolism and virulence
title_short	Analyses of the three 1-Cys Peroxiredoxins from Aspergillus fumigatus reveal that cytosolic Prx1 is central to H2O2 metabolism and virulence
title_full	Analyses of the three 1-Cys Peroxiredoxins from Aspergillus fumigatus reveal that cytosolic Prx1 is central to H2O2 metabolism and virulence
title_fullStr	Analyses of the three 1-Cys Peroxiredoxins from Aspergillus fumigatus reveal that cytosolic Prx1 is central to H2O2 metabolism and virulence
title_full_unstemmed	Analyses of the three 1-Cys Peroxiredoxins from Aspergillus fumigatus reveal that cytosolic Prx1 is central to H2O2 metabolism and virulence
title_sort	analyses of the three 1-cys peroxiredoxins from aspergillus fumigatus reveal that cytosolic prx1 is central to h2o2 metabolism and virulence
publisher	Nature Portfolio
publishDate	2018
url	https://doaj.org/article/76476fbdb8c84c26bedd08eff953e9a9
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Analyses of the three 1-Cys Peroxiredoxins from Aspergillus fumigatus reveal that cytosolic Prx1 is central to H2O2 metabolism and virulence

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