The NorR Regulon Is Critical for <named-content content-type="genus-species">Vibrio cholerae</named-content> Resistance to Nitric Oxide and Sustained Colonization of the Intestines

ABSTRACT 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 ar...

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Autores principales:	Andrew M. Stern, Amanda J. Hay, Zhi Liu, Fiona A. Desland, Juan Zhang, Zengtao Zhong, Jun Zhu
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2012
Materias:	Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/294b82272ecd450aa89812c65dd5303f
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spelling	oai:doaj.org-article:294b82272ecd450aa89812c65dd5303f2021-11-15T15:39:09ZThe NorR Regulon Is Critical for <named-content content-type="genus-species">Vibrio cholerae</named-content> Resistance to Nitric Oxide and Sustained Colonization of the Intestines10.1128/mBio.00013-122150-7511https://doaj.org/article/294b82272ecd450aa89812c65dd5303f2012-05-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mBio.00013-12https://doaj.org/toc/2150-7511ABSTRACT 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 H2O2, 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. IMPORTANCE Little is known about what environmental stresses Vibrio cholerae, the etiologic agent of cholera, encounters during infection, and even less is known about how V. cholerae senses and counters these stresses. Most prior studies of V. cholerae infection relied on the 24-h infant mouse model, which does not allow the analysis of survival over time periods comparable to that of an actual V. cholerae infection. In this study, we used a sustained mouse colonization model to identify nitric oxide resistance as a function critical for the survival of V. cholerae in the intestines and further identified the genes responsible for sensing and detoxifying this stress.Andrew M. SternAmanda J. HayZhi LiuFiona A. DeslandJuan ZhangZengtao ZhongJun ZhuAmerican Society for MicrobiologyarticleMicrobiologyQR1-502ENmBio, Vol 3, Iss 2 (2012)
institution	DOAJ
collection	DOAJ
language	EN
topic	Microbiology QR1-502
spellingShingle	Microbiology QR1-502 Andrew M. Stern Amanda J. Hay Zhi Liu Fiona A. Desland Juan Zhang Zengtao Zhong Jun Zhu The NorR Regulon Is Critical for <named-content content-type="genus-species">Vibrio cholerae</named-content> Resistance to Nitric Oxide and Sustained Colonization of the Intestines
description	ABSTRACT 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 H2O2, 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. IMPORTANCE Little is known about what environmental stresses Vibrio cholerae, the etiologic agent of cholera, encounters during infection, and even less is known about how V. cholerae senses and counters these stresses. Most prior studies of V. cholerae infection relied on the 24-h infant mouse model, which does not allow the analysis of survival over time periods comparable to that of an actual V. cholerae infection. In this study, we used a sustained mouse colonization model to identify nitric oxide resistance as a function critical for the survival of V. cholerae in the intestines and further identified the genes responsible for sensing and detoxifying this stress.
format	article
author	Andrew M. Stern Amanda J. Hay Zhi Liu Fiona A. Desland Juan Zhang Zengtao Zhong Jun Zhu
author_facet	Andrew M. Stern Amanda J. Hay Zhi Liu Fiona A. Desland Juan Zhang Zengtao Zhong Jun Zhu
author_sort	Andrew M. Stern
title	The NorR Regulon Is Critical for <named-content content-type="genus-species">Vibrio cholerae</named-content> Resistance to Nitric Oxide and Sustained Colonization of the Intestines
title_short	The NorR Regulon Is Critical for <named-content content-type="genus-species">Vibrio cholerae</named-content> Resistance to Nitric Oxide and Sustained Colonization of the Intestines
title_full	The NorR Regulon Is Critical for <named-content content-type="genus-species">Vibrio cholerae</named-content> Resistance to Nitric Oxide and Sustained Colonization of the Intestines
title_fullStr	The NorR Regulon Is Critical for <named-content content-type="genus-species">Vibrio cholerae</named-content> Resistance to Nitric Oxide and Sustained Colonization of the Intestines
title_full_unstemmed	The NorR Regulon Is Critical for <named-content content-type="genus-species">Vibrio cholerae</named-content> Resistance to Nitric Oxide and Sustained Colonization of the Intestines
title_sort	norr regulon is critical for <named-content content-type="genus-species">vibrio cholerae</named-content> resistance to nitric oxide and sustained colonization of the intestines
publisher	American Society for Microbiology
publishDate	2012
url	https://doaj.org/article/294b82272ecd450aa89812c65dd5303f
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The NorR Regulon Is Critical for <named-content content-type="genus-species">Vibrio cholerae</named-content> Resistance to Nitric Oxide and Sustained Colonization of the Intestines

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