PMID:15175307

Citation	Dalton, TL and Scott, JR (2004) CovS inactivates CovR and is required for growth under conditions of general stress in Streptococcus pyogenes. J. Bacteriol. 186:3928-37
Abstract	The gram-positive human pathogen Streptococcus pyogenes (group A streptococcus [GAS]) causes diseases ranging from mild and often self-limiting infections of the skin or throat to invasive and life-threatening illnesses. To cause such diverse types of disease, the GAS must be able to sense adverse environments and regulate its gene expression accordingly. The CovR/S two-component signal transduction regulatory system in GAS represses about 15% of the GAS genome, including many genes involved in virulence, in response to the environment. We report that CovR is still able to repress transcription from several promoters in the absence of the putative histidine kinase sensor for this system, CovS. We also show that a phosphorylation site mutant (D53A) of CovR is unable to repress gene expression. In addition, we report that a strain with a nonpolar mutation in CovS does not grow at a low pH, elevated temperature, or high osmolarity. The stress-related phenotypes of the CovS mutant were complemented by expression of covS from a plasmid. Selection for growth of a CovS mutant under stress conditions resulted in isolation of second-site mutations that inactivated covR, indicating that CovR and CovS act in the same pathway. Also, at 40 degrees C in the wild-type strain, CovR appeared to be less active on the promoter tested, which is consistent with the hypothesis that it was partially inactivated by CovS. We suggest that under mild stress conditions, CovS inactivates CovR, either directly or indirectly, and that this inactivation relieves repression of many GAS genes, including the genes needed for growth of GAS under stress conditions and some genes that are necessary for virulence. Growth of many gram-positive bacteria under multiple-stress conditions requires alteration of promoter recognition produced by RNA polymerase association with the general stress response sigma factor, sigma(B). We provide evidence that for GAS, which lacks a sigB ortholog, growth under stress conditions requires the CovR/S two-component regulatory system instead. This two-component system in GAS thus appears to perform a function for which other gram-positive bacteria utilize an alternative sigma factor.
Links	PubMed PMC419969 Online version:10.1128/JB.186.12.3928-3937.2004
Keywords	Amino Acid Sequence; Bacterial Proteins/chemistry; Bacterial Proteins/genetics; Bacterial Proteins/metabolism; Gene Expression Regulation, Bacterial; Heat-Shock Response; Hydrogen-Ion Concentration; Models, Molecular; Molecular Sequence Data; Mutation; Phosphorylation; Protein Kinases/chemistry; Protein Kinases/genetics; Protein Kinases/metabolism; Repressor Proteins/chemistry; Repressor Proteins/genetics; Repressor Proteins/metabolism; Signal Transduction; Streptococcus pyogenes/genetics; Streptococcus pyogenes/growth & development; Streptococcus pyogenes/physiology; Temperature
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Annotations

Gene product	Qualifier	GO Term	Evidence Code	with/from	Aspect	Extension	Notes	Status
STRPY:B3VA60	involved_in	GO:0045892: negative regulation of transcription, DNA-templated	ECO:0000315: mutant phenotype evidence used in manual assertion		P		Seeded From UniProt	complete
STRPY:B3VA60		GO:0045892: negative regulation of transcription, DNA-dependent	ECO:0000315:		P		Figure 2. In the absence of covR, sagA and sda transcripts were upregulated 8.9 fold and 5.3 fold respectively.	complete CACAO 5242

References

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