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. 2001 Jan;183(2):468-75.
doi: 10.1128/JB.183.2.468-475.2001.

In Staphylococcus aureus, fur is an interactive regulator with PerR, contributes to virulence, and Is necessary for oxidative stress resistance through positive regulation of catalase and iron homeostasis

M J Horsburgh  1 , E Ingham, S J Foster
Affiliations

In Staphylococcus aureus, fur is an interactive regulator with PerR, contributes to virulence, and Is necessary for oxidative stress resistance through positive regulation of catalase and iron homeostasis

M J Horsburgh et al. J Bacteriol. 2001 Jan.

Abstract

The Staphylococcus aureus genome encodes three ferric uptake repressor (Fur) homologues: Fur, PerR, and Zur. To determine the exact role of Fur in S VSports手机版. aureus, we inactivated the fur gene by allelic replacement using a tetracycline resistance cassette, creating strain MJH010 (fur). The mutant had a growth defect in rich medium, and this defect was exacerbated in metal-depleted CL medium. This growth defect was partially suppressed by manganous ion, a metal ion with known antioxidant properties. This suggests that the fur mutation leads to an oxidative stress condition. Indeed, MJH010 (fur) has reduced levels of catalase activity resulting from decreased katA transcription. Using a katA-lacZ fusion we have determined that Fur functions, either directly or indirectly, as an iron-dependent positive regulator of katA expression. Transcription of katA is coregulated by Fur and PerR, since in MJH010 (fur) transcription was still repressed by manganese while transcription in MJH201 (fur perR) was unresponsive to the presence of iron or manganese. Siderophore biosynthesis was repressed by iron in 8325-4 (wild-type) but in MJH010 (fur) was constitutive. A number of putative Fur-regulated genes were identified in the incomplete genome databases using known S. aureus Fur box sequences. Of those tested, the sstABCD and sirABC operons and the fhuD2 and orf4 genes were found to have Fur-regulated expression. MJH010 (fur) was attenuated (P<0. 04) in a murine skin abscess model of infection, as was double-mutant MJH201 (fur perR) (P<0. 03). This demonstrates the importance in vivo of iron homeostasis and oxidative stress resistance regulation in S. aureus. .

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"V体育2025版" Figures

FIG. 1
FIG. 1
Growth of 8325-4 (wild type) (■), MJH010 (fur) (▵), and MJH201 (fur perR) (●) in CL medium (no added metals except magnesium) (A), CL with 20 μM manganese chloride (B), and CL with 20 μM iron sulfate (C).
FIG. 2
FIG. 2
(A) Effect of H2O2 (7.5 mM) on washed, exponential-phase cells of 8325-4 (wild type) (■), MJH010 (fur) (▵), MJH201 (fur perR) (▴), and MJH001 (perR) (○). (B) Total catalase activities of washed, lysed stationary-phase cells after growth in CLR medium (white bars), CL with 20 μM manganese chloride (grey bars), or CL medium with 20 μM iron sulfate (black bars).
FIG. 3
FIG. 3
Analysis of transcription from katA-lacZ fusions in different backgrounds during growth in CLR medium. Shown are growth (filled symbols) and expression (open symbols) of MJH006 (katA-lacZ) (A), MJH206 (fur katA-lacZ) (B), and MJH306 (fur perR katA-lacZ) (C) in CLR medium (triangles), CLR medium with 20 μM manganese chloride (diamonds), and CLR medium with 20 μM iron sulfate (circles).
FIG. 4
FIG. 4
Siderophore levels of 8325-4 (wild type) (open bars) and MJH010 (fur) (solid bars) strains after growth in metal-depleted SSD medium with or without manganese chloride or iron sulfate (20 μM each) supplementation.
FIG. 5
FIG. 5
(A) Alignment of the putative Fur boxes identified in the incomplete S. aureus databases (http://www.tigr.org and http://www.genome.ou.edu). Sequences were identified using the Microsoft Word 2000 Find tool by inserting the “any character” function to enable mismatches. (B) The S. aureus consensus sequence was compiled from all of the sequences and is presented as described in reference . The sirA Fur box was taken from reference , the sstA gene name was taken from the sequence with GenBank accession no. AJ005352, the fhuC Fur box was from part of the protected region described in reference , and the PerR consensus sequence was from M. J. Horsburgh et al. (submitted).
FIG. 6
FIG. 6
Effect of Fur on transcription of promoter-lacZ fusions to the fhuD2, orf4, sstA, and sirA genes during growth in CLR medium containing no iron (open bars) or 10 μM iron sulfate (solid bars). Values presented were taken during exponential growth (OD600 = 1) from growth curves sampled throughout growth. The data presented are representative of three independent experiments that showed less than 20% variability.
FIG. 7
FIG. 7
Pathogenicity of S. aureus strains in a murine skin abscess model of infection. Approximately 108 CFU of each strain was inoculated subcutaneously into 6- to 8-week-old BALB/c mice (10 for each strain). Seven days after infection mice were euthanized, lesions were removed and homogenized, and viable bacteria were counted after dilution and growth on BHI agar plates.
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