The Copper-Responsive RicR Regulon Contributes to <named-content content-type="genus-species">Mycobacterium tuberculosis</named-content> Virulence

ABSTRACT As with most life on Earth, the transition metal copper (Cu) is essential for the viability of the human pathogen Mycobacterium tuberculosis. However, infected hosts can also use Cu to control microbial growth. Several Cu-responsive pathways are present in M. tuberculosis, including the reg...

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Autores principales:	Xiaoshan Shi, Richard A. Festa, Thomas R. Ioerger, Susan Butler-Wu, James C. Sacchettini, K. Heran Darwin, Marie I. Samanovic
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2014
Materias:	Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/aa7d1669284643a8868f17587bd8a794
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spelling	oai:doaj.org-article:aa7d1669284643a8868f17587bd8a7942021-11-15T15:45:09ZThe Copper-Responsive RicR Regulon Contributes to <named-content content-type="genus-species">Mycobacterium tuberculosis</named-content> Virulence10.1128/mBio.00876-132150-7511https://doaj.org/article/aa7d1669284643a8868f17587bd8a7942014-02-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mBio.00876-13https://doaj.org/toc/2150-7511ABSTRACT As with most life on Earth, the transition metal copper (Cu) is essential for the viability of the human pathogen Mycobacterium tuberculosis. However, infected hosts can also use Cu to control microbial growth. Several Cu-responsive pathways are present in M. tuberculosis, including the regulated in copper repressor (RicR) regulon, which is unique to pathogenic mycobacteria. In this work, we describe the contribution of each RicR-regulated gene to Cu resistance in vitro and to virulence in animals. We found that the deletion or disruption of individual RicR-regulated genes had no impact on virulence in mice, although several mutants had Cu hypersensitivity. In contrast, a mutant unable to activate the RicR regulon was not only highly susceptible to Cu but also attenuated in mice. Thus, these data suggest that several genes of the RicR regulon are required simultaneously to combat Cu toxicity in vivo or that this regulon is also important for resistance against Cu-independent mechanisms of host defense. IMPORTANCE Mycobacterium tuberculosis is the causative agent of tuberculosis, killing millions of people every year. Therefore, understanding the biology of M. tuberculosis is crucial for the development of new therapies to treat this devastating disease. Our studies reveal that although host-supplied Cu can suppress bacterial growth, M. tuberculosis has a unique pathway, the RicR regulon, to defend against Cu toxicity. These findings suggest that Cu homeostasis pathways in both the host and the pathogen could be exploited for the treatment of tuberculosis.Xiaoshan ShiRichard A. FestaThomas R. IoergerSusan Butler-WuJames C. SacchettiniK. Heran DarwinMarie I. SamanovicAmerican Society for MicrobiologyarticleMicrobiologyQR1-502ENmBio, Vol 5, Iss 1 (2014)
institution	DOAJ
collection	DOAJ
language	EN
topic	Microbiology QR1-502
spellingShingle	Microbiology QR1-502 Xiaoshan Shi Richard A. Festa Thomas R. Ioerger Susan Butler-Wu James C. Sacchettini K. Heran Darwin Marie I. Samanovic The Copper-Responsive RicR Regulon Contributes to <named-content content-type="genus-species">Mycobacterium tuberculosis</named-content> Virulence
description	ABSTRACT As with most life on Earth, the transition metal copper (Cu) is essential for the viability of the human pathogen Mycobacterium tuberculosis. However, infected hosts can also use Cu to control microbial growth. Several Cu-responsive pathways are present in M. tuberculosis, including the regulated in copper repressor (RicR) regulon, which is unique to pathogenic mycobacteria. In this work, we describe the contribution of each RicR-regulated gene to Cu resistance in vitro and to virulence in animals. We found that the deletion or disruption of individual RicR-regulated genes had no impact on virulence in mice, although several mutants had Cu hypersensitivity. In contrast, a mutant unable to activate the RicR regulon was not only highly susceptible to Cu but also attenuated in mice. Thus, these data suggest that several genes of the RicR regulon are required simultaneously to combat Cu toxicity in vivo or that this regulon is also important for resistance against Cu-independent mechanisms of host defense. IMPORTANCE Mycobacterium tuberculosis is the causative agent of tuberculosis, killing millions of people every year. Therefore, understanding the biology of M. tuberculosis is crucial for the development of new therapies to treat this devastating disease. Our studies reveal that although host-supplied Cu can suppress bacterial growth, M. tuberculosis has a unique pathway, the RicR regulon, to defend against Cu toxicity. These findings suggest that Cu homeostasis pathways in both the host and the pathogen could be exploited for the treatment of tuberculosis.
format	article
author	Xiaoshan Shi Richard A. Festa Thomas R. Ioerger Susan Butler-Wu James C. Sacchettini K. Heran Darwin Marie I. Samanovic
author_facet	Xiaoshan Shi Richard A. Festa Thomas R. Ioerger Susan Butler-Wu James C. Sacchettini K. Heran Darwin Marie I. Samanovic
author_sort	Xiaoshan Shi
title	The Copper-Responsive RicR Regulon Contributes to <named-content content-type="genus-species">Mycobacterium tuberculosis</named-content> Virulence
title_short	The Copper-Responsive RicR Regulon Contributes to <named-content content-type="genus-species">Mycobacterium tuberculosis</named-content> Virulence
title_full	The Copper-Responsive RicR Regulon Contributes to <named-content content-type="genus-species">Mycobacterium tuberculosis</named-content> Virulence
title_fullStr	The Copper-Responsive RicR Regulon Contributes to <named-content content-type="genus-species">Mycobacterium tuberculosis</named-content> Virulence
title_full_unstemmed	The Copper-Responsive RicR Regulon Contributes to <named-content content-type="genus-species">Mycobacterium tuberculosis</named-content> Virulence
title_sort	copper-responsive ricr regulon contributes to <named-content content-type="genus-species">mycobacterium tuberculosis</named-content> virulence
publisher	American Society for Microbiology
publishDate	2014
url	https://doaj.org/article/aa7d1669284643a8868f17587bd8a794
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The Copper-Responsive RicR Regulon Contributes to <named-content content-type="genus-species">Mycobacterium tuberculosis</named-content> Virulence

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