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Involvement of a 1-Cys Peroxiredoxin in Bacterial Virulence
The killing of bacterial pathogens by macrophages occurs via the oxidative burst and bacteria have evolved to overcome this challenge and survive, using several virulence and defense strategies, including antioxidant mechanisms. We show here that the 1-Cys peroxiredoxin LsfA from the opportunistic p...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2014
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4199769/ https://www.ncbi.nlm.nih.gov/pubmed/25329795 http://dx.doi.org/10.1371/journal.ppat.1004442 |
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author | Kaihami, Gilberto Hideo de Almeida, José Roberto Fogaça dos Santos, Suelen Silvana Netto, Luis Eduardo Soares de Almeida, Sandro Rogério Baldini, Regina Lúcia |
author_facet | Kaihami, Gilberto Hideo de Almeida, José Roberto Fogaça dos Santos, Suelen Silvana Netto, Luis Eduardo Soares de Almeida, Sandro Rogério Baldini, Regina Lúcia |
author_sort | Kaihami, Gilberto Hideo |
collection | PubMed |
description | The killing of bacterial pathogens by macrophages occurs via the oxidative burst and bacteria have evolved to overcome this challenge and survive, using several virulence and defense strategies, including antioxidant mechanisms. We show here that the 1-Cys peroxiredoxin LsfA from the opportunistic pathogen Pseudomonas aeruginosa is endowed with thiol-dependent peroxidase activity that protects the bacteria from H(2)O(2) and that this protein is implicated in pathogenicity. LsfA belongs to the poorly studied Prx6 subfamily of peroxiredoxins. The function of these peroxiredoxins has not been characterized in bacteria, and their contribution to host-pathogen interactions remains unknown. Infection of macrophages with the lsfA mutant strains resulted in higher levels of the cytokine TNF-α production due to the activation of the NF-kB and MAPK pathways, that are partially inhibited by the wild-type P. aeruginosa strain. A redox fluorescent probe was more oxidized in the lsfA mutant-infected macrophages than it was in the macrophages infected with the wild-type strain, suggesting that the oxidative burst was overstimulated in the absence of LsfA. Although no differences in the phagocytosis rates were observed when macrophages were infected with wild-type and mutant bacteria in a gentamicin exclusion assay, a higher number of wild-type bacterial cells was found in the supernatant. This difference was not observed when macrophages were pre-treated with a NADPH oxidase inhibitor, confirming the role of LsfA in the bacterial resistance to ROS generated via NADPH oxidase. In an acute pneumonia model, mice infected with the mutant strains presented higher cytokine release in the lungs and increased activated neutrophil recruitment, with reduced bacterial burden and improved survival rates compared to mice infected with the wild-type bacteria. LsfA is the first bacterial 1-Cys Prx shown to modulate host immune responses and its characterization will allow a better understanding of the role of redox signaling in host-pathogen interactions. |
format | Online Article Text |
id | pubmed-4199769 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2014 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-41997692014-10-21 Involvement of a 1-Cys Peroxiredoxin in Bacterial Virulence Kaihami, Gilberto Hideo de Almeida, José Roberto Fogaça dos Santos, Suelen Silvana Netto, Luis Eduardo Soares de Almeida, Sandro Rogério Baldini, Regina Lúcia PLoS Pathog Research Article The killing of bacterial pathogens by macrophages occurs via the oxidative burst and bacteria have evolved to overcome this challenge and survive, using several virulence and defense strategies, including antioxidant mechanisms. We show here that the 1-Cys peroxiredoxin LsfA from the opportunistic pathogen Pseudomonas aeruginosa is endowed with thiol-dependent peroxidase activity that protects the bacteria from H(2)O(2) and that this protein is implicated in pathogenicity. LsfA belongs to the poorly studied Prx6 subfamily of peroxiredoxins. The function of these peroxiredoxins has not been characterized in bacteria, and their contribution to host-pathogen interactions remains unknown. Infection of macrophages with the lsfA mutant strains resulted in higher levels of the cytokine TNF-α production due to the activation of the NF-kB and MAPK pathways, that are partially inhibited by the wild-type P. aeruginosa strain. A redox fluorescent probe was more oxidized in the lsfA mutant-infected macrophages than it was in the macrophages infected with the wild-type strain, suggesting that the oxidative burst was overstimulated in the absence of LsfA. Although no differences in the phagocytosis rates were observed when macrophages were infected with wild-type and mutant bacteria in a gentamicin exclusion assay, a higher number of wild-type bacterial cells was found in the supernatant. This difference was not observed when macrophages were pre-treated with a NADPH oxidase inhibitor, confirming the role of LsfA in the bacterial resistance to ROS generated via NADPH oxidase. In an acute pneumonia model, mice infected with the mutant strains presented higher cytokine release in the lungs and increased activated neutrophil recruitment, with reduced bacterial burden and improved survival rates compared to mice infected with the wild-type bacteria. LsfA is the first bacterial 1-Cys Prx shown to modulate host immune responses and its characterization will allow a better understanding of the role of redox signaling in host-pathogen interactions. Public Library of Science 2014-10-16 /pmc/articles/PMC4199769/ /pubmed/25329795 http://dx.doi.org/10.1371/journal.ppat.1004442 Text en © 2014 Kaihami et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited. |
spellingShingle | Research Article Kaihami, Gilberto Hideo de Almeida, José Roberto Fogaça dos Santos, Suelen Silvana Netto, Luis Eduardo Soares de Almeida, Sandro Rogério Baldini, Regina Lúcia Involvement of a 1-Cys Peroxiredoxin in Bacterial Virulence |
title | Involvement of a 1-Cys Peroxiredoxin in Bacterial Virulence |
title_full | Involvement of a 1-Cys Peroxiredoxin in Bacterial Virulence |
title_fullStr | Involvement of a 1-Cys Peroxiredoxin in Bacterial Virulence |
title_full_unstemmed | Involvement of a 1-Cys Peroxiredoxin in Bacterial Virulence |
title_short | Involvement of a 1-Cys Peroxiredoxin in Bacterial Virulence |
title_sort | involvement of a 1-cys peroxiredoxin in bacterial virulence |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4199769/ https://www.ncbi.nlm.nih.gov/pubmed/25329795 http://dx.doi.org/10.1371/journal.ppat.1004442 |
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