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...
| Main Authors: | , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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American Society for Microbiology
2017-06-01
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| Series: | mSphere |
| Subjects: | |
| Online Access: | https://journals.asm.org/doi/10.1128/mSphere.00082-17 |
| _version_ | 1818568823003938816 |
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| 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 |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-12-14T06:40:08Z |
| format | Article |
| id | doaj.art-60c8556789154f8cabe92ef3914e72d7 |
| institution | Directory Open Access Journal |
| issn | 2379-5042 |
| language | English |
| last_indexed | 2024-12-14T06:40:08Z |
| publishDate | 2017-06-01 |
| publisher | American Society for Microbiology |
| record_format | Article |
| series | mSphere |
| spelling | doaj.art-60c8556789154f8cabe92ef3914e72d72022-12-21T23:13:15ZengAmerican Society for MicrobiologymSphere2379-50422017-06-012310.1128/mSphere.00082-17Sulfide Homeostasis and Nitroxyl Intersect via Formation of Reactive Sulfur Species in <named-content content-type="genus-species">Staphylococcus aureus</named-content>Hui Peng0Jiangchuan Shen1Katherine A. Edmonds2Justin L. Luebke3Anne K. Hickey4Lauren D. Palmer5Feng-Ming James Chang6Kevin A. Bruce7Thomas E. Kehl-Fie8Eric P. Skaar9David P. Giedroc10Department of Chemistry, Indiana University, Bloomington, Indiana, USADepartment of Chemistry, Indiana University, Bloomington, Indiana, USADepartment of Chemistry, Indiana University, Bloomington, Indiana, USADepartment of Chemistry, Indiana University, Bloomington, Indiana, USADepartment of Chemistry, Indiana University, Bloomington, Indiana, USADepartment of Pathology, Microbiology, and Immunology, Vanderbilt University Medical Center, Nashville, Tennessee, USADepartment of Chemistry, Indiana University, Bloomington, Indiana, USADepartment of Biology, Indiana University, Bloomington, Indiana, USADepartment of Pathology, Microbiology, and Immunology, Vanderbilt University Medical Center, Nashville, Tennessee, USADepartment of Pathology, Microbiology, and Immunology, Vanderbilt University Medical Center, Nashville, Tennessee, USADepartment of Chemistry, Indiana University, Bloomington, Indiana, USAABSTRACT 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.https://journals.asm.org/doi/10.1128/mSphere.00082-17hydrogen sulfidenitric oxidenitroxylpersulfidereactive nitrogen speciesreactive sulfur species |
| spellingShingle | 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> mSphere hydrogen sulfide nitric oxide nitroxyl persulfide reactive nitrogen species reactive sulfur species |
| title | 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_short | 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 |
| topic | hydrogen sulfide nitric oxide nitroxyl persulfide reactive nitrogen species reactive sulfur species |
| url | https://journals.asm.org/doi/10.1128/mSphere.00082-17 |
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