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The NorR Regulon Is Critical for Vibrio cholerae Resistance to Nitric Oxide and Sustained Colonization of the Intestines

Vibrio cholerae, the cause of an often fatal infectious diarrhea, remains a large global public health threat. Little is known about the challenges V. cholerae encounters during colonization of the intestines, which genes are important for overcoming these challenges, and how these genes are regulat...

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Autores principales: Stern, Andrew M., Hay, Amanda J., Liu, Zhi, Desland, Fiona A., Zhang, Juan, Zhong, Zengtao, Zhu, Jun
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Society of Microbiology 2012
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3345576/
https://www.ncbi.nlm.nih.gov/pubmed/22511349
http://dx.doi.org/10.1128/mBio.00013-12
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author Stern, Andrew M.
Hay, Amanda J.
Liu, Zhi
Desland, Fiona A.
Zhang, Juan
Zhong, Zengtao
Zhu, Jun
author_facet Stern, Andrew M.
Hay, Amanda J.
Liu, Zhi
Desland, Fiona A.
Zhang, Juan
Zhong, Zengtao
Zhu, Jun
author_sort Stern, Andrew M.
collection PubMed
description Vibrio cholerae, the cause of an often fatal infectious diarrhea, remains a large global public health threat. Little is known about the challenges V. cholerae encounters during colonization of the intestines, which genes are important for overcoming these challenges, and how these genes are regulated. In this study, we examined the V. cholerae response to nitric oxide (NO), an antibacterial molecule derived during infection from various sources, including host inducible NO synthase (iNOS). We demonstrate that the regulatory protein NorR regulates the expression of NO detoxification genes hmpA and nnrS, and that all three are critical for resisting low levels of NO stress under microaerobic conditions in vitro. We also show that prxA, a gene previously thought to be important for NO detoxification, plays no role in NO resistance under microaerobic conditions and is upregulated by H(2)O(2), not NO. Furthermore, in an adult mouse model of prolonged colonization, hmpA and norR were important for the resistance of both iNOS- and non-iNOS-derived stresses. Our data demonstrate that NO detoxification systems play a critical role in the survival of V. cholerae under microaerobic conditions resembling those of an infectious setting and during colonization of the intestines over time periods similar to that of an actual V. cholerae infection.
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spelling pubmed-33455762012-05-09 The NorR Regulon Is Critical for Vibrio cholerae Resistance to Nitric Oxide and Sustained Colonization of the Intestines Stern, Andrew M. Hay, Amanda J. Liu, Zhi Desland, Fiona A. Zhang, Juan Zhong, Zengtao Zhu, Jun mBio Research Article Vibrio cholerae, the cause of an often fatal infectious diarrhea, remains a large global public health threat. Little is known about the challenges V. cholerae encounters during colonization of the intestines, which genes are important for overcoming these challenges, and how these genes are regulated. In this study, we examined the V. cholerae response to nitric oxide (NO), an antibacterial molecule derived during infection from various sources, including host inducible NO synthase (iNOS). We demonstrate that the regulatory protein NorR regulates the expression of NO detoxification genes hmpA and nnrS, and that all three are critical for resisting low levels of NO stress under microaerobic conditions in vitro. We also show that prxA, a gene previously thought to be important for NO detoxification, plays no role in NO resistance under microaerobic conditions and is upregulated by H(2)O(2), not NO. Furthermore, in an adult mouse model of prolonged colonization, hmpA and norR were important for the resistance of both iNOS- and non-iNOS-derived stresses. Our data demonstrate that NO detoxification systems play a critical role in the survival of V. cholerae under microaerobic conditions resembling those of an infectious setting and during colonization of the intestines over time periods similar to that of an actual V. cholerae infection. American Society of Microbiology 2012-04-17 /pmc/articles/PMC3345576/ /pubmed/22511349 http://dx.doi.org/10.1128/mBio.00013-12 Text en Copyright © 2012 Stern et al. http://creativecommons.org/licenses/by-nc-sa/3.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution-Noncommercial-Share Alike 3.0 Unported License (http://creativecommons.org/licenses/by-nc-sa/3.0/) , which permits unrestricted noncommercial use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Stern, Andrew M.
Hay, Amanda J.
Liu, Zhi
Desland, Fiona A.
Zhang, Juan
Zhong, Zengtao
Zhu, Jun
The NorR Regulon Is Critical for Vibrio cholerae Resistance to Nitric Oxide and Sustained Colonization of the Intestines
title The NorR Regulon Is Critical for Vibrio cholerae Resistance to Nitric Oxide and Sustained Colonization of the Intestines
title_full The NorR Regulon Is Critical for Vibrio cholerae Resistance to Nitric Oxide and Sustained Colonization of the Intestines
title_fullStr The NorR Regulon Is Critical for Vibrio cholerae Resistance to Nitric Oxide and Sustained Colonization of the Intestines
title_full_unstemmed The NorR Regulon Is Critical for Vibrio cholerae Resistance to Nitric Oxide and Sustained Colonization of the Intestines
title_short The NorR Regulon Is Critical for Vibrio cholerae Resistance to Nitric Oxide and Sustained Colonization of the Intestines
title_sort norr regulon is critical for vibrio cholerae resistance to nitric oxide and sustained colonization of the intestines
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3345576/
https://www.ncbi.nlm.nih.gov/pubmed/22511349
http://dx.doi.org/10.1128/mBio.00013-12
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