A Response Regulator That Represses Transcriptionof Several Virulence Operons in the Group A Streptococcus

摘要

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 capsulesynthesis, and because CsrA-CsrB is a global regulatory system inEscherichia coli whose mechanism is unrelated to that ofthese genes in GAS, the locus has been renamed covR, for“control of virulence genes” in GAS. Transcription of thecovR operon was also increased in the nonpolar insertionmutant, indicating that CovR represses its own synthesis as well. Allphenotypes of the covR nonpolar insertion mutant werecomplemented by the covR gene on a plasmid. CovR acts onoperons expressed both in exponential and in stationary phase,demonstrating that the CovR-CovS pathway is separate from growthphase-dependent regulation in GAS. Therefore, CovR is the firstmultiple-gene repressor of virulence factors described for thisimportant human pathogen.