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Infection and Immunity, June 2001, p. 3744-3754, Vol. 69, No. 6
Department of Molecular Biology and
Biotechnology, University of Sheffield, Western Bank, Sheffield S10
2TN,1 and Department of Microbiology,
University of Leeds, Leeds,3 England, and
Microbiology and Tumour Biology Centre, Karolinska
Institute, 17177 Stockholm, Sweden2
Received 4 January 2001/Returned for modification 12 February
2001/Accepted 14 March 2001
The Staphylococcus aureus genome encodes three
ferric uptake regulator (Fur) homologues: Fur, PerR, and Zur. To
determine the exact role of PerR, we inactivated the gene by allelic
replacement using a kanamycin cassette, creating strain MJH001
(perR). PerR was found to control transcription of the
genes encoding the oxidative stress resistance proteins catalase
(KatA), alkyl hydroperoxide reductase (AhpCF), bacterioferritin
comigratory protein (Bcp), and thioredoxin reductase (TrxB).
Furthermore, PerR regulates transcription of the genes encoding the
iron storage proteins ferritin (Ftn) and the ferritin-like Dps
homologue, MrgA. Transcription of perR was
autoregulated, and PerR repressed transcription of the iron homeostasis
regulator Fur, which is a positive regulator of catalase expression.
PerR functions as a manganese-dependent, transcriptional repressor of
the identified regulon. Elevated iron concentrations produced induction
of the PerR regulon. PerR may act as a peroxide sensor, since addition
of external hydrogen peroxide to 8325-4 (wild type) resulted in
increased transcription of most of the PerR regulon, except for
fur and perR itself. The PerR-regulated
katA gene encodes the sole catalase of S.
aureus, which is an important starvation survival determinant
but is surprisingly not required for pathogenicity in a murine skin
abscess model of infection. In contrast, PerR is not necessary for
starvation survival but is required for full virulence
(P < 0.005) in this model of infection. PerR of
S. aureus may act as a redox sentinel protein during
infection, analogous to the in vitro activities of OxyR and PerR of
Escherichia coli and Bacillus subtilis,
respectively. However, it differs in its response to the metal
balance within the cell and has the added capability of regulating iron
uptake and storage.
0019-9567/01/$04.00+0 DOI: 10.1128/IAI.69.6.3744-3754.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.
PerR Controls Oxidative Stress Resistance and Iron Storage
Proteins and Is Required for Virulence in Staphylococcus
aureus
*
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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