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Journal of Bacteriology, January 2001, p. 468-475, Vol. 183, No. 2
Department of Molecular Biology and
Biotechnology, University of Sheffield, Sheffield S10
2TN,1 and Department of
Microbiology, University of Leeds, Leeds,2
England
Received 26 July 2000/Accepted 23 October 2000
The Staphylococcus aureus genome encodes three ferric
uptake repressor (Fur) homologues: Fur, PerR, and Zur. To determine the
exact role of Fur in S. 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.
0021-9193/01/$04.00+0 DOI: 10.1128/JB.183.2.468-475.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.
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
*
Corresponding author. Mailing address: Department of
Molecular Biology and Biotechnology, University of Sheffield, Western Bank, Sheffield S10 2TN, England. Phone: 44 0114 222 4411. Fax: 44 0114 272 8697. E-mail: S.Foster{at}sheffield.ac.uk.
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