This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Dalton, T. L.
Right arrow Articles by Scott, J. R.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Dalton, T. L.
Right arrow Articles by Scott, J. R.

 Previous Article  |  Next Article 

Journal of Bacteriology, June 2004, p. 3928-3937, Vol. 186, No. 12
0021-9193/04/$08.00+0     DOI: 10.1128/JB.186.12.3928-3937.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

CovS Inactivates CovR and Is Required for Growth under Conditions of General Stress in Streptococcus pyogenes

Tracy L. Dalton and June R. Scott*

Department of Microbiology and Immunology, Emory University School of Medicine, Atlanta, Georgia 30322

Received 12 December 2003/ Accepted 11 March 2004

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°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.

* 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.

Journal of Bacteriology, June 2004, p. 3928-3937, Vol. 186, No. 12
0021-9193/04/$08.00+0     DOI: 10.1128/JB.186.12.3928-3937.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Chiang-Ni, C., Zheng, P.-X., Ho, Y.-R., Wu, H.-M., Chuang, W.-J., Lin, Y.-S., Lin, M.-T., Liu, C.-C., Wu, J.-J. (2009). emm1/Sequence Type 28 Strains of Group A Streptococci That Express covR at Early Stationary Phase Are Associated with Increased Growth and Earlier SpeB Secretion. J. Clin. Microbiol. 47: 3161-3169 [Abstract] [Full Text]  
  • Trevino, J., Perez, N., Ramirez-Pena, E., Liu, Z., Shelburne, S. A. III, Musser, J. M., Sumby, P. (2009). CovS Simultaneously Activates and Inhibits the CovR-Mediated Repression of Distinct Subsets of Group A Streptococcus Virulence Factor-Encoding Genes. Infect. Immun. 77: 3141-3149 [Abstract] [Full Text]  
  • Churchward, G., Bates, C., Gusa, A. A., Stringer, V., Scott, J. R. (2009). Regulation of streptokinase expression by CovR/S in Streptococcus pyogenes: CovR acts through a single high-affinity binding site. Microbiology 155: 566-575 [Abstract] [Full Text]  
  • Froehlich, B. J., Bates, C., Scott, J. R. (2009). Streptococcus pyogenes CovRS Mediates Growth in Iron Starvation and in the Presence of the Human Cationic Antimicrobial Peptide LL-37. J. Bacteriol. 191: 673-677 [Abstract] [Full Text]  
  • Zhang, J., Biswas, I. (2009). A phenotypic microarray analysis of a Streptococcus mutans liaS mutant. Microbiology 155: 61-68 [Abstract] [Full Text]  
  • Gryllos, I., Tran-Winkler, H. J., Cheng, M.-F., Chung, H., Bolcome, R. III, Lu, W., Lehrer, R. I., Wessels, M. R. (2008). Induction of group A Streptococcus virulence by a human antimicrobial peptide. Proc. Natl. Acad. Sci. USA 105: 16755-16760 [Abstract] [Full Text]  
  • Leday, T. V., Gold, K. M., Kinkel, T. L., Roberts, S. A., Scott, J. R., McIver, K. S. (2008). TrxR, a New CovR-Repressed Response Regulator That Activates the Mga Virulence Regulon in Group A Streptococcus. Infect. Immun. 76: 4659-4668 [Abstract] [Full Text]  
  • Kinkel, T. L., McIver, K. S. (2008). CcpA-Mediated Repression of Streptolysin S Expression and Virulence in the Group A Streptococcus. Infect. Immun. 76: 3451-3463 [Abstract] [Full Text]  
  • Chong, P., Drake, L., Biswas, I. (2008). Modulation of covR Expression in Streptococcus mutans UA159. J. Bacteriol. 190: 4478-4488 [Abstract] [Full Text]  
  • Dunning, D. W., McCall, L. W., Powell, W. F., Arscott, W. T., McConocha, E. M., McClurg, C. J., Goodman, S. D., Spatafora, G. A. (2008). SloR modulation of the Streptococcus mutans acid tolerance response involves the GcrR response regulator as an essential intermediary. Microbiology 154: 1132-1143 [Abstract] [Full Text]  
  • Jiang, S.-M., Ishmael, N., Hotopp, J. D., Puliti, M., Tissi, L., Kumar, N., Cieslewicz, M. J., Tettelin, H., Wessels, M. R. (2008). Variation in the Group B Streptococcus CsrRS Regulon and Effects on Pathogenicity. J. Bacteriol. 190: 1956-1965 [Abstract] [Full Text]  
  • Biswas, I., Drake, L., Erkina, D., Biswas, S. (2008). Involvement of Sensor Kinases in the Stress Tolerance Response of Streptococcus mutans. J. Bacteriol. 190: 68-77 [Abstract] [Full Text]  
  • Biswas, I., Drake, L., Biswas, S. (2007). Regulation of gbpC Expression in Streptococcus mutans. J. Bacteriol. 189: 6521-6531 [Abstract] [Full Text]  
  • Pfeiler, E. A., Azcarate-Peril, M. A., Klaenhammer, T. R. (2007). Characterization of a Novel Bile-Inducible Operon Encoding a Two-Component Regulatory System in Lactobacillus acidophilus. J. Bacteriol. 189: 4624-4634 [Abstract] [Full Text]  
  • Shelburne, S. A. III, Okorafor, N., Sitkiewicz, I., Sumby, P., Keith, D., Patel, P., Austin, C., Graviss, E. A., Musser, J. M. (2007). Regulation of Polysaccharide Utilization Contributes to the Persistence of Group A Streptococcus in the Oropharynx. Infect. Immun. 75: 2981-2990 [Abstract] [Full Text]  
  • Barnett, T. C., Bugrysheva, J. V., Scott, J. R. (2007). Role of mRNA Stability in Growth Phase Regulation of Gene Expression in the Group A Streptococcus. J. Bacteriol. 189: 1866-1873 [Abstract] [Full Text]  
  • Roberts, S. A., Churchward, G. G., Scott, J. R. (2007). Unraveling the Regulatory Network in Streptococcus pyogenes: the Global Response Regulator CovR Represses rivR Directly. J. Bacteriol. 189: 1459-1463 [Abstract] [Full Text]  
  • Gusa, A. A., Froehlich, B. J., Desai, D., Stringer, V., Scott, J. R. (2007). CovR Activation of the Dipeptide Permease Promoter (PdppA) in Group A Streptococcus. J. Bacteriol. 189: 1407-1416 [Abstract] [Full Text]  
  • Burne, R. A., Bessen, D. E., Broadbent, J. R., Claverys, J.-P. (2007). The Seventh International Conference on the Genetics of Streptococci, Lactococci, and Enterococci. J. Bacteriol. 189: 1209-1218 [Full Text]  
  • Graham, M. R., Virtaneva, K., Porcella, S. F., Gardner, D. J., Long, R. D., Welty, D. M., Barry, W. T., Johnson, C. A., Parkins, L. D., Wright, F. A., Musser, J. M. (2006). Analysis of the Transcriptome of Group A Streptococcus in Mouse Soft Tissue Infection. Am. J. Pathol. 169: 927-942 [Abstract] [Full Text]  
  • Shelburne, S. A. III, Sumby, P., Sitkiewicz, I., Okorafor, N., Granville, C., Patel, P., Voyich, J., Hull, R., DeLeo, F. R., Musser, J. M. (2006). Maltodextrin utilization plays a key role in the ability of group a streptococcus to colonize the oropharynx.. Infect. Immun. 74: 4605-4614 [Abstract] [Full Text]  
  • Gusa, A. A., Gao, J., Stringer, V., Churchward, G., Scott, J. R. (2006). Phosphorylation of the Group A Streptococcal CovR Response Regulator Causes Dimerization and Promoter-Specific Recruitment by RNA Polymerase. J. Bacteriol. 188: 4620-4626 [Abstract] [Full Text]  
  • Biswas, S., Biswas, I. (2006). Regulation of the Glucosyltransferase (gtfBC) Operon by CovR in Streptococcus mutans. J. Bacteriol. 188: 988-998 [Abstract] [Full Text]  
  • Loughman, J. A., Caparon, M. (2006). Regulation of SpeB in Streptococcus pyogenes by pH and NaCl: a Model for In Vivo Gene Expression. J. Bacteriol. 188: 399-408 [Abstract] [Full Text]  
  • Dalton, T. L., Collins, J. T., Barnett, T. C., Scott, J. R. (2006). RscA, a Member of the MDR1 Family of Transporters, Is Repressed by CovR and Required for Growth of Streptococcus pyogenes under Heat Stress. J. Bacteriol. 188: 77-85 [Abstract] [Full Text]  
  • Gao, J., Gusa, A. A., Scott, J. R., Churchward, G. (2005). Binding of the Global Response Regulator Protein CovR to the sag Promoter of Streptococcus pyogenes Reveals a New Mode of CovR-DNA Interaction. J. Biol. Chem. 280: 38948-38956 [Abstract] [Full Text]  
  • Graham, M. R., Virtaneva, K., Porcella, S. F., Barry, W. T., Gowen, B. B., Johnson, C. R., Wright, F. A., Musser, J. M. (2005). Group A Streptococcus Transcriptome Dynamics during Growth in Human Blood Reveals Bacterial Adaptive and Survival Strategies. Am. J. Pathol. 166: 455-465 [Abstract] [Full Text]  
  • Chaussee, M. A., Callegari, E. A., Chaussee, M. S. (2004). Rgg Regulates Growth Phase-Dependent Expression of Proteins Associated with Secondary Metabolism and Stress in Streptococcus pyogenes. J. Bacteriol. 186: 7091-7099 [Abstract] [Full Text]  


Copyright © 2009 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»