title: MntR modulates expression of the PerR regulon and superoxide resistance in Staphylococcus aureus through control of manganese uptake.
abstract: 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 respectively. 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.
authors.affiliation: Department of Molecular Biology and Biotechnology, University of Sheffield, Western Bank, Sheffield S10 2TN, UK.
authors.forename: Malcolm J
authors.initials: MJ
authors.lastname: Horsburgh
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Wharton
authors.forename: Alan G
authors.initials: AG
authors.lastname: Cox
authors.forename: Eileen
authors.initials: E
authors.lastname: Ingham
authors.forename: Sharon
authors.initials: S
authors.lastname: Peacock
authors.forename: Simon J
authors.initials: SJ
authors.lastname: Foster
mesh_terms: D000818:Animals; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism*; D001483:Base Sequence; D004730:Endothelium, Vascular / Q000166:cytology / Q000378:metabolism / Q000382:microbiology; D015964:Gene Expression Regulation, Bacterial; D005798:Genes, Bacterial; D017930:Genes, Reporter; D006540:Herbicides / Q000494:pharmacology; D006706:Homeostasis; D006801:Humans; D008345:Manganese / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D010269:Paraquat / Q000494:pharmacology; D011401:Promoter Regions, Genetic; D011993:Recombinant Fusion Proteins; D018085:Regulon / Q000235:genetics*; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism*; D013211:Staphylococcus aureus / Q000187:drug effects / Q000235:genetics* / Q000378:metabolism* / Q000472:pathogenicity; D013481:Superoxides / Q000378:metabolism*; D014157:Transcription Factors
chemical_list: D001426:Bacterial Proteins; D006540:Herbicides; C433792:MntR protein, bacteria; D011993:Recombinant Fusion Proteins; D012097:Repressor Proteins; D014157:Transcription Factors; C122138:peroxide repressor proteins; D013481:Superoxides; D008345:Manganese; D010269:Paraquat