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MntR modulates expression of the PerR regulon and superoxide resistance in Staphylococcus aureus through control of manganese uptake
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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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In the citing paper
“In addition to regulation by MntR, mntABC is negatively regulated by PerR, a manganese and iron-dependent Fur homologue that controls responses to oxidative stress [144, 145].”
From Metal ion acquisition in Staphylococcus aureus: overcoming nutritional immunity (2012) · cites this paper as [144]
Experimental — accuracy not yet measuredIn the citing paper
“In contrast, mutation of mntH does not lead to an appreciable growth defect in metal-depleted media”
From Metal ion acquisition in Staphylococcus aureus: overcoming nutritional immunity (2012) · cites this paper as [144]
In the citing paper
“The S. aureus genome encodes MntABC-type (mntABC) and Nramp-type (mntH) manganese transporters, both of which have been functionally characterized.”
From Metal ion acquisition in Staphylococcus aureus: overcoming nutritional immunity (2012) · cites this paper as [144]
In the citing paper
“In manganese-replete conditions, transcription of mntABC is repressed by MntR.”
From Metal ion acquisition in Staphylococcus aureus: overcoming nutritional immunity (2012) · cites this paper as [144]
In the citing paper
“Mutation of mntA in S. aureus results in a reduced growth rate in metal-depleted minimal media, a phenotype that is reversible upon addition of manganese.”
From Metal ion acquisition in Staphylococcus aureus: overcoming nutritional immunity (2012) · cites this paper as [144]
In the citing paper
“Deletion of mntR leads to constitutive transcription of mntABC irrespective of manganese levels.”
From Metal ion acquisition in Staphylococcus aureus: overcoming nutritional immunity (2012) · cites this paper as [144]
In the citing paper
“suggesting that MntABC may be the dominant manganese transporter in S. aureus under in vitro conditions [144].”
From Metal ion acquisition in Staphylococcus aureus: overcoming nutritional immunity (2012) · cites this paper as [144]
In the citing paper
“The transcriptional regulator MntR affects expression of both mntABC and mntH.”
From Metal ion acquisition in Staphylococcus aureus: overcoming nutritional immunity (2012) · cites this paper as [144]
In the citing paper
“In S. aureus, mutation of mntA, mntH, or mntR in the laboratory strain 8325-4 does not lead to a significant reduction in bacterial recovery in a murine skin abscess model.”
From Metal ion acquisition in Staphylococcus aureus: overcoming nutritional immunity (2012) · cites this paper as [144]
In the citing paper
“Additionally, S. aureus employs superoxide dismutase-independent mechanisms to detoxify superoxide, a process that is also dependent on manganese [144].”
From Metal ion acquisition in Staphylococcus aureus: overcoming nutritional immunity (2012) · cites this paper as [144]
In the citing paper
“Disruption of mntA, mntH, mntR, or both mntA and mntH also significantly reduces intracellular survival in human endothelial cells [144].”
From Metal ion acquisition in Staphylococcus aureus: overcoming nutritional immunity (2012) · cites this paper as [144]
In the citing paper
“In contrast, concurrent inactivation of mntA and mntH significantly decreases bacterial recovery in this model.”
From Metal ion acquisition in Staphylococcus aureus: overcoming nutritional immunity (2012) · cites this paper as [144]
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Metadata
- Authors
- Horsburgh, M. J., Wharton, S. J., Cox, A. G., Ingham, E., Peacock, S., & Foster, S. J.
- Affiliations
- University of Sheffield (GB)
- University of Leeds (GB)
- John Radcliffe Hospital (GB)
- Corresponding author
- Foster, Simon J.
- Venue
- Molecular Microbiology
- Publisher
- Wiley
- Published
- 2002-05-23
- Volume
- 44
- Issue
- 5
- Pages
- 1269-1286
- ISSN
- 0950-382X (ISSN-L)
- 1365-2958
- OpenAlex
- W2154476329
- Cited by
- 228
- References
- 65
- Citations by year
- 2026: 7 · 2025: 7 · 2024: 7 · 2023: 4 · 2022: 4 · 2021: 8 · 2020: 15 · 2019: 15 · 2018: 11 · 2017: 9 · 2016: 12 · 2015: 13 · 2014: 9 · 2013: 14 · 2012: 8
- FWCI
- 4.49
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Molecular Microbiology (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Bacterial Genetics and Biotechnology
- Health Sciences › Medicine › Infectious Diseases › Antimicrobial Resistance in Staphylococcus
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Fungal and yeast genetics research
- Keywords
- MntR, PerR, Staphylococcus aureus, manganese uptake, MntH, oxidative stress resistance, fur, kata, ferritin, metal homeostasis, gene expression regulation, virulence
- MeSH terms
- Animals, Bacterial Proteins, Base Sequence, Endothelium, Vascular, Genes, Bacterial, Herbicides, Homeostasis, Humans, Manganese, Mice, Inbred BALB C, Molecular Sequence Data, Paraquat, Promoter Regions, Genetic, Recombinant Fusion Proteins, Repressor Proteins, Staphylococcus aureus, Superoxides, Transcription Factors, Gene Expression Regulation, Bacterial, Genes, Reporter, Regulon, Mice
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