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Journal of Bacteriology, February 2001, p. 1113-1123, Vol. 183, No. 4
0021-9193/01/$04.00+0 DOI: 10.1128/JB.183.4.1113-1123.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.
Identification of a Novel Two-Component Regulatory
System That Acts in Global Regulation of Virulence Factors of
Staphylococcus aureus
Jeremy M.
Yarwood,
John K.
McCormick, and
Patrick
M.
Schlievert*
Department of Microbiology, University of
Minnesota Medical School, Minneapolis, Minnesota 55455
Received 25 August 2000/Accepted 16 November 2000
We have previously demonstrated that the presence of oxygen is
necessary for the production of toxic shock syndrome toxin 1 (TSST-1)
by Staphylococcus aureus in vitro. To investigate the mechanism by which oxygen might regulate toxin production, we identified homologs in S. aureus of the Bacillus
subtilis resDE genes. The two-component regulatory system encoded
by resDE, ResD-ResE, has been implicated in the global
regulation of aerobic and anaerobic respiratory metabolism in B. subtilis. We have designated the S. aureus homologs
srrAB (staphylococcal respiratory response). The effects of
srrAB expression on expression of RNAIII (the effector molecule of the agr locus) and on production of TSST-1 (an
exotoxin) and protein A (a surface-associated virulence factor) were
investigated. Expression of RNAIII was inversely related to expression
of srrAB. Disruption of srrB resulted in
increased levels of RNAIII, while expression of srrAB in
trans on a multicopy plasmid resulted in repression of
RNAIII transcription, particularly in microaerobic conditions.
Disruption of srrB resulted in decreased production of
TSST-1 under microaerobic conditions and, to a lesser extent, under
aerobic conditions as well. Overexpression of srrAB
resulted in nearly complete repression of TSST-1 production in both
microaerobic and aerobic conditions. Protein A production by the
srrB mutant was upregulated in microaerobic conditions and
decreased in aerobic conditions. Protein A production was restored to
nearly wild-type levels by complementation of srrAB into
the null mutant. These results indicate that the putative two-component
system encoded by srrAB, SrrA-SrrB, acts in the global
regulation of staphylococcal virulence factors, and may repress
virulence factors under low-oxygen conditions. Furthermore,
srrAB may provide a mechanistic link between respiratory
metabolism, environmental signals, and regulation of virulence factors
in S. aureus.
*
Corresponding author. Mailing address: Department of
Microbiology, Medical School, University of Minnesota, Box 196 FUMC, 420 Delaware St. SE, Minneapolis, MN 55455. Phone: (612) 624-9471. Fax:
(612) 626-0623. E-mail: pats{at}lenti.med.umn.edu.
Journal of Bacteriology, February 2001, p. 1113-1123, Vol. 183, No. 4
0021-9193/01/$04.00+0 DOI: 10.1128/JB.183.4.1113-1123.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.
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