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Lack of OxyR and KatG Results in Extreme Susceptibility of Francisella tularensis LVS to Oxidative Stress and Marked Attenuation In vivo

Francisella tularensis is an intracellular bacterium and as such is expected to encounter a continuous attack by reactive oxygen species (ROS) in its intracellular habitat and efficiently coping with oxidative stress is therefore essential for its survival. The oxidative stress response system of F....

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Autores principales: Honn, Marie, Lindgren, Helena, Bharath, Gurram K., Sjöstedt, Anders
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5258697/
https://www.ncbi.nlm.nih.gov/pubmed/28174696
http://dx.doi.org/10.3389/fcimb.2017.00014
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author Honn, Marie
Lindgren, Helena
Bharath, Gurram K.
Sjöstedt, Anders
author_facet Honn, Marie
Lindgren, Helena
Bharath, Gurram K.
Sjöstedt, Anders
author_sort Honn, Marie
collection PubMed
description Francisella tularensis is an intracellular bacterium and as such is expected to encounter a continuous attack by reactive oxygen species (ROS) in its intracellular habitat and efficiently coping with oxidative stress is therefore essential for its survival. The oxidative stress response system of F. tularensis is complex and includes multiple antioxidant enzymes and pathways, including the transcriptional regulator OxyR and the H(2)O(2)-decomposing enzyme catalase, encoded by katG. The latter is regulated by OxyR. A deletion of either of these genes, however, does not severely compromise the virulence of F. tularensis and we hypothesized that if the bacterium would be deficient of both catalase and OxyR, then the oxidative defense and virulence of F. tularensis would become severely hampered. To test this hypothesis, we generated a double deletion mutant, ΔoxyR/ΔkatG, of F. tularensis LVS and compared its phenotype to the parental LVS strain and the corresponding single deletion mutants. In accordance with the hypothesis, ΔoxyR/ΔkatG was distinctly more susceptible than ΔoxyR and ΔkatG to H(2)O(2), ONOO(−), and [Formula: see text] , moreover, it hardly grew in mouse-derived BMDM or in mice, whereas ΔkatG and ΔoxyR grew as well as F. tularensis LVS in BMDM and exhibited only slight attenuation in mice. Altogether, the results demonstrate the importance of catalase and OxyR for a robust oxidative stress defense system and that they act cooperatively. The lack of both functions render F. tularensis severely crippled to handle oxidative stress and also much attenuated for intracellular growth and virulence.
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spelling pubmed-52586972017-02-07 Lack of OxyR and KatG Results in Extreme Susceptibility of Francisella tularensis LVS to Oxidative Stress and Marked Attenuation In vivo Honn, Marie Lindgren, Helena Bharath, Gurram K. Sjöstedt, Anders Front Cell Infect Microbiol Microbiology Francisella tularensis is an intracellular bacterium and as such is expected to encounter a continuous attack by reactive oxygen species (ROS) in its intracellular habitat and efficiently coping with oxidative stress is therefore essential for its survival. The oxidative stress response system of F. tularensis is complex and includes multiple antioxidant enzymes and pathways, including the transcriptional regulator OxyR and the H(2)O(2)-decomposing enzyme catalase, encoded by katG. The latter is regulated by OxyR. A deletion of either of these genes, however, does not severely compromise the virulence of F. tularensis and we hypothesized that if the bacterium would be deficient of both catalase and OxyR, then the oxidative defense and virulence of F. tularensis would become severely hampered. To test this hypothesis, we generated a double deletion mutant, ΔoxyR/ΔkatG, of F. tularensis LVS and compared its phenotype to the parental LVS strain and the corresponding single deletion mutants. In accordance with the hypothesis, ΔoxyR/ΔkatG was distinctly more susceptible than ΔoxyR and ΔkatG to H(2)O(2), ONOO(−), and [Formula: see text] , moreover, it hardly grew in mouse-derived BMDM or in mice, whereas ΔkatG and ΔoxyR grew as well as F. tularensis LVS in BMDM and exhibited only slight attenuation in mice. Altogether, the results demonstrate the importance of catalase and OxyR for a robust oxidative stress defense system and that they act cooperatively. The lack of both functions render F. tularensis severely crippled to handle oxidative stress and also much attenuated for intracellular growth and virulence. Frontiers Media S.A. 2017-01-24 /pmc/articles/PMC5258697/ /pubmed/28174696 http://dx.doi.org/10.3389/fcimb.2017.00014 Text en Copyright © 2017 Honn, Lindgren, Bharath and Sjöstedt. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Microbiology
Honn, Marie
Lindgren, Helena
Bharath, Gurram K.
Sjöstedt, Anders
Lack of OxyR and KatG Results in Extreme Susceptibility of Francisella tularensis LVS to Oxidative Stress and Marked Attenuation In vivo
title Lack of OxyR and KatG Results in Extreme Susceptibility of Francisella tularensis LVS to Oxidative Stress and Marked Attenuation In vivo
title_full Lack of OxyR and KatG Results in Extreme Susceptibility of Francisella tularensis LVS to Oxidative Stress and Marked Attenuation In vivo
title_fullStr Lack of OxyR and KatG Results in Extreme Susceptibility of Francisella tularensis LVS to Oxidative Stress and Marked Attenuation In vivo
title_full_unstemmed Lack of OxyR and KatG Results in Extreme Susceptibility of Francisella tularensis LVS to Oxidative Stress and Marked Attenuation In vivo
title_short Lack of OxyR and KatG Results in Extreme Susceptibility of Francisella tularensis LVS to Oxidative Stress and Marked Attenuation In vivo
title_sort lack of oxyr and katg results in extreme susceptibility of francisella tularensis lvs to oxidative stress and marked attenuation in vivo
topic Microbiology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5258697/
https://www.ncbi.nlm.nih.gov/pubmed/28174696
http://dx.doi.org/10.3389/fcimb.2017.00014
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