Sulfide Homeostasis and Nitroxyl Intersect via Formation of Reactive Sulfur Species in <named-content content-type="genus-species">Staphylococcus aureus</named-content>

ABSTRACT Staphylococcus aureus is a commensal human pathogen and a major cause of nosocomial infections. As gaseous signaling molecules, endogenous hydrogen sulfide (H2S) and nitric oxide (NO·) protect S. aureus from antibiotic stress synergistically, which we propose involves the intermediacy of ni...

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Autores principales:	Hui Peng, Jiangchuan Shen, Katherine A. Edmonds, Justin L. Luebke, Anne K. Hickey, Lauren D. Palmer, Feng-Ming James Chang, Kevin A. Bruce, Thomas E. Kehl-Fie, Eric P. Skaar, David P. Giedroc
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2017
Materias:	hydrogen sulfide nitric oxide nitroxyl persulfide reactive nitrogen species reactive sulfur species Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/60c8556789154f8cabe92ef3914e72d7
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spelling	oai:doaj.org-article:60c8556789154f8cabe92ef3914e72d72021-11-15T15:21:47ZSulfide Homeostasis and Nitroxyl Intersect via Formation of Reactive Sulfur Species in <named-content content-type="genus-species">Staphylococcus aureus</named-content>10.1128/mSphere.00082-172379-5042https://doaj.org/article/60c8556789154f8cabe92ef3914e72d72017-06-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mSphere.00082-17https://doaj.org/toc/2379-5042ABSTRACT Staphylococcus aureus is a commensal human pathogen and a major cause of nosocomial infections. As gaseous signaling molecules, endogenous hydrogen sulfide (H2S) and nitric oxide (NO·) protect S. aureus from antibiotic stress synergistically, which we propose involves the intermediacy of nitroxyl (HNO). Here, we examine the effect of exogenous sulfide and HNO on the transcriptome and the formation of low-molecular-weight (LMW) thiol persulfides of bacillithiol, cysteine, and coenzyme A as representative of reactive sulfur species (RSS) in wild-type and ΔcstR strains of S. aureus. CstR is a per- and polysulfide sensor that controls the expression of a sulfide oxidation and detoxification system. As anticipated, exogenous sulfide induces the cst operon but also indirectly represses much of the CymR regulon which controls cysteine metabolism. A zinc limitation response is also observed, linking sulfide homeostasis to zinc bioavailability. Cellular RSS levels impact the expression of a number of virulence factors, including the exotoxins, particularly apparent in the ΔcstR strain. HNO, like sulfide, induces the cst operon as well as other genes regulated by exogenous sulfide, a finding that is traced to a direct reaction of CstR with HNO and to an endogenous perturbation in cellular RSS, possibly originating from disassembly of Fe-S clusters. More broadly, HNO induces a transcriptomic response to Fe overload, Cu toxicity, and reactive oxygen species and reactive nitrogen species and shares similarity with the sigB regulon. This work reveals an H2S/NO· interplay in S. aureus that impacts transition metal homeostasis and virulence gene expression. IMPORTANCE Hydrogen sulfide (H2S) is a toxic molecule and a recently described gasotransmitter in vertebrates whose function in bacteria is not well understood. In this work, we describe the transcriptomic response of the major human pathogen Staphylococcus aureus to quantified changes in levels of cellular organic reactive sulfur species, which are effector molecules involved in H2S signaling. We show that nitroxyl (HNO), a recently described signaling intermediate proposed to originate from the interplay of H2S and nitric oxide, also induces changes in cellular sulfur speciation and transition metal homeostasis, thus linking sulfide homeostasis to an adaptive response to antimicrobial reactive nitrogen species.Hui PengJiangchuan ShenKatherine A. EdmondsJustin L. LuebkeAnne K. HickeyLauren D. PalmerFeng-Ming James ChangKevin A. BruceThomas E. Kehl-FieEric P. SkaarDavid P. GiedrocAmerican Society for Microbiologyarticlehydrogen sulfidenitric oxidenitroxylpersulfidereactive nitrogen speciesreactive sulfur speciesMicrobiologyQR1-502ENmSphere, Vol 2, Iss 3 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	hydrogen sulfide nitric oxide nitroxyl persulfide reactive nitrogen species reactive sulfur species Microbiology QR1-502
spellingShingle	hydrogen sulfide nitric oxide nitroxyl persulfide reactive nitrogen species reactive sulfur species Microbiology QR1-502 Hui Peng Jiangchuan Shen Katherine A. Edmonds Justin L. Luebke Anne K. Hickey Lauren D. Palmer Feng-Ming James Chang Kevin A. Bruce Thomas E. Kehl-Fie Eric P. Skaar David P. Giedroc Sulfide Homeostasis and Nitroxyl Intersect via Formation of Reactive Sulfur Species in <named-content content-type="genus-species">Staphylococcus aureus</named-content>
description	ABSTRACT Staphylococcus aureus is a commensal human pathogen and a major cause of nosocomial infections. As gaseous signaling molecules, endogenous hydrogen sulfide (H2S) and nitric oxide (NO·) protect S. aureus from antibiotic stress synergistically, which we propose involves the intermediacy of nitroxyl (HNO). Here, we examine the effect of exogenous sulfide and HNO on the transcriptome and the formation of low-molecular-weight (LMW) thiol persulfides of bacillithiol, cysteine, and coenzyme A as representative of reactive sulfur species (RSS) in wild-type and ΔcstR strains of S. aureus. CstR is a per- and polysulfide sensor that controls the expression of a sulfide oxidation and detoxification system. As anticipated, exogenous sulfide induces the cst operon but also indirectly represses much of the CymR regulon which controls cysteine metabolism. A zinc limitation response is also observed, linking sulfide homeostasis to zinc bioavailability. Cellular RSS levels impact the expression of a number of virulence factors, including the exotoxins, particularly apparent in the ΔcstR strain. HNO, like sulfide, induces the cst operon as well as other genes regulated by exogenous sulfide, a finding that is traced to a direct reaction of CstR with HNO and to an endogenous perturbation in cellular RSS, possibly originating from disassembly of Fe-S clusters. More broadly, HNO induces a transcriptomic response to Fe overload, Cu toxicity, and reactive oxygen species and reactive nitrogen species and shares similarity with the sigB regulon. This work reveals an H2S/NO· interplay in S. aureus that impacts transition metal homeostasis and virulence gene expression. IMPORTANCE Hydrogen sulfide (H2S) is a toxic molecule and a recently described gasotransmitter in vertebrates whose function in bacteria is not well understood. In this work, we describe the transcriptomic response of the major human pathogen Staphylococcus aureus to quantified changes in levels of cellular organic reactive sulfur species, which are effector molecules involved in H2S signaling. We show that nitroxyl (HNO), a recently described signaling intermediate proposed to originate from the interplay of H2S and nitric oxide, also induces changes in cellular sulfur speciation and transition metal homeostasis, thus linking sulfide homeostasis to an adaptive response to antimicrobial reactive nitrogen species.
format	article
author	Hui Peng Jiangchuan Shen Katherine A. Edmonds Justin L. Luebke Anne K. Hickey Lauren D. Palmer Feng-Ming James Chang Kevin A. Bruce Thomas E. Kehl-Fie Eric P. Skaar David P. Giedroc
author_facet	Hui Peng Jiangchuan Shen Katherine A. Edmonds Justin L. Luebke Anne K. Hickey Lauren D. Palmer Feng-Ming James Chang Kevin A. Bruce Thomas E. Kehl-Fie Eric P. Skaar David P. Giedroc
author_sort	Hui Peng
title	Sulfide Homeostasis and Nitroxyl Intersect via Formation of Reactive Sulfur Species in <named-content content-type="genus-species">Staphylococcus aureus</named-content>
title_short	Sulfide Homeostasis and Nitroxyl Intersect via Formation of Reactive Sulfur Species in <named-content content-type="genus-species">Staphylococcus aureus</named-content>
title_full	Sulfide Homeostasis and Nitroxyl Intersect via Formation of Reactive Sulfur Species in <named-content content-type="genus-species">Staphylococcus aureus</named-content>
title_fullStr	Sulfide Homeostasis and Nitroxyl Intersect via Formation of Reactive Sulfur Species in <named-content content-type="genus-species">Staphylococcus aureus</named-content>
title_full_unstemmed	Sulfide Homeostasis and Nitroxyl Intersect via Formation of Reactive Sulfur Species in <named-content content-type="genus-species">Staphylococcus aureus</named-content>
title_sort	sulfide homeostasis and nitroxyl intersect via formation of reactive sulfur species in <named-content content-type="genus-species">staphylococcus aureus</named-content>
publisher	American Society for Microbiology
publishDate	2017
url	https://doaj.org/article/60c8556789154f8cabe92ef3914e72d7
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Sulfide Homeostasis and Nitroxyl Intersect via Formation of Reactive Sulfur Species in <named-content content-type="genus-species">Staphylococcus aureus</named-content>

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