MntR modulates expression of the PerR regulon and superoxide resistance in Staphylococcus aureus through control of manganese uptake

Summary The Staphylococcus aureus DtxR‐like protein, MntR, controls expression of the mntABC and mntH genes, which encode putative manganese transporters. Mutation of mntABC produced a growth defect in metal‐depleted medium and increased sensitivity to intracellularly generated superoxide radicals....

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Veröffentlicht in:Molecular microbiology 2002-06, Vol.44 (5), p.1269-1286
Hauptverfasser: Horsburgh, Malcolm J., Wharton, Stephen J., Cox, Alan G., Ingham, Eileen, Peacock, Sharon, Foster, Simon J.
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container_end_page 1286
container_issue 5
container_start_page 1269
container_title Molecular microbiology
container_volume 44
creator Horsburgh, Malcolm J.
Wharton, Stephen J.
Cox, Alan G.
Ingham, Eileen
Peacock, Sharon
Foster, Simon J.
description Summary The Staphylococcus aureus DtxR‐like protein, MntR, controls expression of the mntABC and mntH genes, which encode putative manganese transporters. Mutation of mntABC produced a growth defect in metal‐depleted medium and increased sensitivity to intracellularly generated superoxide radicals. These phenotypes resulted from diminished uptake of manganese and were rescued by the addition of excess Mn(II). Resistance to superoxide was incompletely rescued by Mn(II) for STE035 (mntA mntH), and the strain had reduced virulence in a murine abscess model of infection. Expression of mntABC was repressed by Mn(II) in an MntR‐dependent manner, which contrasts with the expression of mntH that was not repressed in elevated Mn(II) and was decreased in an mntR mutant. This demonstrates that MntR acts as a negative and positive regulator of these loci re‐spectively. PerR, the peroxide resistance regulon repressor, acts with MntR to control the expression of mntABC and manganese uptake. The expression of the PerR‐regulated genes, katA (catalase), ftn (ferritin) and fur (ferric uptake regulator), was diminished in STE031 (mntR) when grown in excess Mn(II). Therefore, the control of Mn(II)‐regulated members of the PerR regulon and the Fur protein is modulated by MntR through its control of Mn(II) uptake. The co‐ordinated regulation of metal ion homeostasis and oxidative stress resistance via the regulators MntR, PerR and Fur of S. aureus is discussed.
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Mutation of mntABC produced a growth defect in metal‐depleted medium and increased sensitivity to intracellularly generated superoxide radicals. These phenotypes resulted from diminished uptake of manganese and were rescued by the addition of excess Mn(II). Resistance to superoxide was incompletely rescued by Mn(II) for STE035 (mntA mntH), and the strain had reduced virulence in a murine abscess model of infection. Expression of mntABC was repressed by Mn(II) in an MntR‐dependent manner, which contrasts with the expression of mntH that was not repressed in elevated Mn(II) and was decreased in an mntR mutant. This demonstrates that MntR acts as a negative and positive regulator of these loci re‐spectively. PerR, the peroxide resistance regulon repressor, acts with MntR to control the expression of mntABC and manganese uptake. The expression of the PerR‐regulated genes, katA (catalase), ftn (ferritin) and fur (ferric uptake regulator), was diminished in STE031 (mntR) when grown in excess Mn(II). Therefore, the control of Mn(II)‐regulated members of the PerR regulon and the Fur protein is modulated by MntR through its control of Mn(II) uptake. The co‐ordinated regulation of metal ion homeostasis and oxidative stress resistance via the regulators MntR, PerR and Fur of S. aureus is discussed.</description><identifier>ISSN: 0950-382X</identifier><identifier>EISSN: 1365-2958</identifier><identifier>DOI: 10.1046/j.1365-2958.2002.02944.x</identifier><identifier>PMID: 12028379</identifier><language>eng</language><publisher>Oxford, UK: Blackwell Science Ltd</publisher><subject>Animals ; Bacterial Proteins - genetics ; Bacterial Proteins - metabolism ; Base Sequence ; Endothelium, Vascular - cytology ; Endothelium, Vascular - metabolism ; Endothelium, Vascular - microbiology ; Gene Expression Regulation, Bacterial ; Genes, Bacterial ; Genes, Reporter ; Herbicides - pharmacology ; Homeostasis ; Humans ; Manganese - metabolism ; Mice ; Mice, Inbred BALB C ; Molecular Sequence Data ; Paraquat - pharmacology ; Promoter Regions, Genetic ; Recombinant Fusion Proteins ; Regulon - genetics ; Repressor Proteins - genetics ; Repressor Proteins - metabolism ; Staphylococcus aureus - drug effects ; Staphylococcus aureus - genetics ; Staphylococcus aureus - metabolism ; Staphylococcus aureus - pathogenicity ; Superoxides - metabolism ; Transcription Factors</subject><ispartof>Molecular microbiology, 2002-06, Vol.44 (5), p.1269-1286</ispartof><rights>Copyright Blackwell Scientific Publications Ltd. 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Mutation of mntABC produced a growth defect in metal‐depleted medium and increased sensitivity to intracellularly generated superoxide radicals. These phenotypes resulted from diminished uptake of manganese and were rescued by the addition of excess Mn(II). Resistance to superoxide was incompletely rescued by Mn(II) for STE035 (mntA mntH), and the strain had reduced virulence in a murine abscess model of infection. Expression of mntABC was repressed by Mn(II) in an MntR‐dependent manner, which contrasts with the expression of mntH that was not repressed in elevated Mn(II) and was decreased in an mntR mutant. This demonstrates that MntR acts as a negative and positive regulator of these loci re‐spectively. PerR, the peroxide resistance regulon repressor, acts with MntR to control the expression of mntABC and manganese uptake. The expression of the PerR‐regulated genes, katA (catalase), ftn (ferritin) and fur (ferric uptake regulator), was diminished in STE031 (mntR) when grown in excess Mn(II). Therefore, the control of Mn(II)‐regulated members of the PerR regulon and the Fur protein is modulated by MntR through its control of Mn(II) uptake. 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Mutation of mntABC produced a growth defect in metal‐depleted medium and increased sensitivity to intracellularly generated superoxide radicals. These phenotypes resulted from diminished uptake of manganese and were rescued by the addition of excess Mn(II). Resistance to superoxide was incompletely rescued by Mn(II) for STE035 (mntA mntH), and the strain had reduced virulence in a murine abscess model of infection. Expression of mntABC was repressed by Mn(II) in an MntR‐dependent manner, which contrasts with the expression of mntH that was not repressed in elevated Mn(II) and was decreased in an mntR mutant. This demonstrates that MntR acts as a negative and positive regulator of these loci re‐spectively. PerR, the peroxide resistance regulon repressor, acts with MntR to control the expression of mntABC and manganese uptake. The expression of the PerR‐regulated genes, katA (catalase), ftn (ferritin) and fur (ferric uptake regulator), was diminished in STE031 (mntR) when grown in excess Mn(II). Therefore, the control of Mn(II)‐regulated members of the PerR regulon and the Fur protein is modulated by MntR through its control of Mn(II) uptake. The co‐ordinated regulation of metal ion homeostasis and oxidative stress resistance via the regulators MntR, PerR and Fur of S. aureus is discussed.</abstract><cop>Oxford, UK</cop><pub>Blackwell Science Ltd</pub><pmid>12028379</pmid><doi>10.1046/j.1365-2958.2002.02944.x</doi><tpages>18</tpages><oa>free_for_read</oa></addata></record>
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source Wiley Free Content; MEDLINE; Wiley Online Library Journals Frontfile Complete; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; Free Full-Text Journals in Chemistry
subjects Animals
Bacterial Proteins - genetics
Bacterial Proteins - metabolism
Base Sequence
Endothelium, Vascular - cytology
Endothelium, Vascular - metabolism
Endothelium, Vascular - microbiology
Gene Expression Regulation, Bacterial
Genes, Bacterial
Genes, Reporter
Herbicides - pharmacology
Homeostasis
Humans
Manganese - metabolism
Mice
Mice, Inbred BALB C
Molecular Sequence Data
Paraquat - pharmacology
Promoter Regions, Genetic
Recombinant Fusion Proteins
Regulon - genetics
Repressor Proteins - genetics
Repressor Proteins - metabolism
Staphylococcus aureus - drug effects
Staphylococcus aureus - genetics
Staphylococcus aureus - metabolism
Staphylococcus aureus - pathogenicity
Superoxides - metabolism
Transcription Factors
title MntR modulates expression of the PerR regulon and superoxide resistance in Staphylococcus aureus through control of manganese uptake
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