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Journal of Bacteriology, June 1999, p. 3649-3657, Vol. 181, No. 12
Department of Microbiology and Immunology,
Emory University School of Medicine, Atlanta, Georgia 30322
Received 8 February 1999/Accepted 7 April 1999
A search for homologs of the Bacillus subtilis PhoP
response regulator in the group A streptococcus (GAS) genome revealed three good candidates. Inactivation of one of these, recently identified as csrR (J. C. Levin and M. R. Wessels, Mol. Microbiol. 30:209-219, 1998), caused the strain to
produce mucoid colonies and to increase transcription of
hasA, the first gene in the operon for capsule synthesis.
We report here that a nonpolar insertion in this gene also increased
transcription of ska (encoding streptokinase), sagA (streptolysin S), and speMF (mitogenic
factor) but did not affect transcription of slo
(streptolysin O), mga (multiple gene regulator of GAS),
emm (M protein), scpA (complement C5a
peptidase), or speB or speC (pyrogenic
exotoxins B and C). The amounts of streptokinase, streptolysin S, and
capsule paralleled the levels of transcription of their genes in all
cases. Because CsrR represses genes unrelated to those for capsule
synthesis, and because CsrA-CsrB is a global regulatory system in
Escherichia coli whose mechanism is unrelated to that of
these genes in GAS, the locus has been renamed covR, for
"control of virulence genes" in GAS. Transcription of the
covR operon was also increased in the nonpolar insertion mutant, indicating that CovR represses its own synthesis as well. All
phenotypes of the covR nonpolar insertion mutant were
complemented by the covR gene on a plasmid. CovR acts on
operons expressed both in exponential and in stationary phase,
demonstrating that the CovR-CovS pathway is separate from growth
phase-dependent regulation in GAS. Therefore, CovR is the first
multiple-gene repressor of virulence factors described for this
important human pathogen.
0021-9193/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.
A Response Regulator That Represses Transcription
of Several Virulence Operons in the Group A Streptococcus
*
Corresponding author. Mailing address: Department of
Microbiology and Immunology, Emory University School of Medicine,
Atlanta, GA 30322. Phone: (404) 727-0402. Fax: (404) 727-8999. E-mail: scott{at}microbio.emory.edu.
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