The <named-content content-type="genus-species">Staphylococcus aureus</named-content> SrrAB Two-Component System Promotes Resistance to Nitrosative Stress and Hypoxia

ABSTRACT Staphylococcus aureus is both a commensal and a pathogen of the human host. Survival in the host environment requires resistance to host-derived nitric oxide (NO·). However, S. aureus lacks the NO·-sensing transcriptional regulator NsrR that is used by many bacteria to sense and respond t...

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Autores principales:	Traci L. Kinkel, Christelle M. Roux, Paul M. Dunman, Ferric C. Fang
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2013
Materias:	Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/4545abfdaa694a0c9d44033f1ead6309
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spelling	oai:doaj.org-article:4545abfdaa694a0c9d44033f1ead63092021-11-15T15:42:32ZThe <named-content content-type="genus-species">Staphylococcus aureus</named-content> SrrAB Two-Component System Promotes Resistance to Nitrosative Stress and Hypoxia10.1128/mBio.00696-132150-7511https://doaj.org/article/4545abfdaa694a0c9d44033f1ead63092013-12-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mBio.00696-13https://doaj.org/toc/2150-7511ABSTRACT Staphylococcus aureus is both a commensal and a pathogen of the human host. Survival in the host environment requires resistance to host-derived nitric oxide (NO·). However, S. aureus lacks the NO·-sensing transcriptional regulator NsrR that is used by many bacteria to sense and respond to NO·. In this study, we show that S. aureus is able to sense and respond to both NO· and hypoxia by means of the SrrAB two-component system (TCS). Analysis of the S. aureus transcriptome during nitrosative stress demonstrates the expression of SrrAB-dependent genes required for cytochrome biosynthesis and assembly (qoxABCD, cydAB, hemABCX), anaerobic metabolism (pflAB, adhE, nrdDG), iron-sulfur cluster repair (scdA), and NO· detoxification (hmp). Targeted mutations in SrrAB-regulated loci show that hmp and qoxABCD are required for NO· resistance, whereas nrdDG is specifically required for anaerobic growth. We also show that SrrAB is required for survival in static biofilms, most likely due to oxygen limitation. Activation by hypoxia, NO·, or a qoxABCD quinol oxidase mutation suggests that the SrrAB TCS senses impaired electron flow in the electron transport chain rather than directly interacting with NO· in the manner of NsrR. Nevertheless, like NsrR, SrrAB achieves the physiological goals of selectively expressing hmp in the presence of NO· and minimizing the potential for Fenton chemistry. Activation of the SrrAB regulon allows S. aureus to maintain energy production and essential biosynthetic processes, repair damage, and detoxify NO· in diverse host environments. IMPORTANCE The Hmp flavohemoglobin is required for nitric oxide resistance and is widely distributed in bacteria. Hmp expression must be tightly regulated, because expression under aerobic conditions in the absence of nitric oxide can exacerbate oxidative stress. In most organisms, hmp expression is controlled by the Fe-S cluster-containing repressor NsrR, but this transcriptional regulator is absent in the human pathogen Staphylococcus aureus. We show here that S. aureus achieves hmp regulation in response to nitric oxide and oxygen limitation by placing it under the control of the SrrAB two-component system, which senses reduced electron flow through the respiratory chain. This provides a striking example of convergent evolution, in which the common physiological goals of responding to nitrosative stress while minimizing Fenton chemistry are achieved by distinct regulatory mechanisms.Traci L. KinkelChristelle M. RouxPaul M. DunmanFerric C. FangAmerican Society for MicrobiologyarticleMicrobiologyQR1-502ENmBio, Vol 4, Iss 6 (2013)
institution	DOAJ
collection	DOAJ
language	EN
topic	Microbiology QR1-502
spellingShingle	Microbiology QR1-502 Traci L. Kinkel Christelle M. Roux Paul M. Dunman Ferric C. Fang The <named-content content-type="genus-species">Staphylococcus aureus</named-content> SrrAB Two-Component System Promotes Resistance to Nitrosative Stress and Hypoxia
description	ABSTRACT Staphylococcus aureus is both a commensal and a pathogen of the human host. Survival in the host environment requires resistance to host-derived nitric oxide (NO·). However, S. aureus lacks the NO·-sensing transcriptional regulator NsrR that is used by many bacteria to sense and respond to NO·. In this study, we show that S. aureus is able to sense and respond to both NO· and hypoxia by means of the SrrAB two-component system (TCS). Analysis of the S. aureus transcriptome during nitrosative stress demonstrates the expression of SrrAB-dependent genes required for cytochrome biosynthesis and assembly (qoxABCD, cydAB, hemABCX), anaerobic metabolism (pflAB, adhE, nrdDG), iron-sulfur cluster repair (scdA), and NO· detoxification (hmp). Targeted mutations in SrrAB-regulated loci show that hmp and qoxABCD are required for NO· resistance, whereas nrdDG is specifically required for anaerobic growth. We also show that SrrAB is required for survival in static biofilms, most likely due to oxygen limitation. Activation by hypoxia, NO·, or a qoxABCD quinol oxidase mutation suggests that the SrrAB TCS senses impaired electron flow in the electron transport chain rather than directly interacting with NO· in the manner of NsrR. Nevertheless, like NsrR, SrrAB achieves the physiological goals of selectively expressing hmp in the presence of NO· and minimizing the potential for Fenton chemistry. Activation of the SrrAB regulon allows S. aureus to maintain energy production and essential biosynthetic processes, repair damage, and detoxify NO· in diverse host environments. IMPORTANCE The Hmp flavohemoglobin is required for nitric oxide resistance and is widely distributed in bacteria. Hmp expression must be tightly regulated, because expression under aerobic conditions in the absence of nitric oxide can exacerbate oxidative stress. In most organisms, hmp expression is controlled by the Fe-S cluster-containing repressor NsrR, but this transcriptional regulator is absent in the human pathogen Staphylococcus aureus. We show here that S. aureus achieves hmp regulation in response to nitric oxide and oxygen limitation by placing it under the control of the SrrAB two-component system, which senses reduced electron flow through the respiratory chain. This provides a striking example of convergent evolution, in which the common physiological goals of responding to nitrosative stress while minimizing Fenton chemistry are achieved by distinct regulatory mechanisms.
format	article
author	Traci L. Kinkel Christelle M. Roux Paul M. Dunman Ferric C. Fang
author_facet	Traci L. Kinkel Christelle M. Roux Paul M. Dunman Ferric C. Fang
author_sort	Traci L. Kinkel
title	The <named-content content-type="genus-species">Staphylococcus aureus</named-content> SrrAB Two-Component System Promotes Resistance to Nitrosative Stress and Hypoxia
title_short	The <named-content content-type="genus-species">Staphylococcus aureus</named-content> SrrAB Two-Component System Promotes Resistance to Nitrosative Stress and Hypoxia
title_full	The <named-content content-type="genus-species">Staphylococcus aureus</named-content> SrrAB Two-Component System Promotes Resistance to Nitrosative Stress and Hypoxia
title_fullStr	The <named-content content-type="genus-species">Staphylococcus aureus</named-content> SrrAB Two-Component System Promotes Resistance to Nitrosative Stress and Hypoxia
title_full_unstemmed	The <named-content content-type="genus-species">Staphylococcus aureus</named-content> SrrAB Two-Component System Promotes Resistance to Nitrosative Stress and Hypoxia
title_sort	<named-content content-type="genus-species">staphylococcus aureus</named-content> srrab two-component system promotes resistance to nitrosative stress and hypoxia
publisher	American Society for Microbiology
publishDate	2013
url	https://doaj.org/article/4545abfdaa694a0c9d44033f1ead6309
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The <named-content content-type="genus-species">Staphylococcus aureus</named-content> SrrAB Two-Component System Promotes Resistance to Nitrosative Stress and Hypoxia

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