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 Iyer, R.
Right arrow Articles by Camilli, A.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Iyer, R.
Right arrow Articles by Camilli, A.

 Previous Article  |  Next Article 

Journal of Bacteriology, December 2005, p. 8340-8349, Vol. 187, No. 24
0021-9193/05/$08.00+0     doi:10.1128/JB.187.24.8340-8349.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

Catabolite Control Protein A (CcpA) Contributes to Virulence and Regulation of Sugar Metabolism in Streptococcus pneumoniae

Ramkumar Iyer,2 Nitin S. Baliga,3 and Andrew Camilli1,2*

Howard Hughes Medical Institute,1 Department of Molecular Biology & Microbiology, Tufts University, 136 Harrison Avenue, Boston, Massachusetts 02111,2 Institute for Systems Biology, 1441 N. 34th Street, Seattle, Washington 981033

Received 8 July 2005/ Accepted 2 October 2005

We characterized the role of catabolite control protein A (ccpA) in the physiology and virulence of Streptococcus pneumoniae. S. pneumoniae has a large percentage of its genome devoted to sugar uptake and metabolism, and therefore, regulation of these processes is likely to be crucial for fitness in the nasopharynx and may play a role during invasive disease. In many bacteria, carbon catabolite repression (CCR) is central to such regulation, influencing hierarchical sugar utilization and growth rates. CcpA is the major transcriptional regulator in CCR in several gram-positive bacteria. We show that CcpA functions in CCR of lactose-inducible ß-galactosidase activity in S. pneumoniae. CCR of maltose-inducible {alpha}-glucosidase, raffinose-inducible {alpha}-galactosidase, and cellobiose-inducible ß-glucosidase is unaffected in the ccpA strain, suggesting that other regulators, possibly redundant with CcpA, control these systems. The ccpA strain is severely attenuated for nasopharyngeal colonization and lung infection in the mouse, establishing its role in fitness on these mucosal surfaces. Comparison of the cell wall fraction of the ccpA and wild-type strains shows that CcpA regulates many proteins in this compartment that are involved in central and intermediary metabolism, a subset of which are required for survival and multiplication in vivo. Both in vitro and in vivo defects were complemented by providing ccpA in trans. Our results demonstrate that CcpA, though not a global regulator of CCR in S. pneumoniae, is required for colonization of the nasopharynx and survival and multiplication in the lung.

* Corresponding author. Mailing address: Department of Molecular Biology & Microbiology, Tufts University, 136 Harrison Avenue, Boston, MA 02111. Phone: (617) 636-2144. Fax: (617) 636-2175. E-mail: andrew.camilli{at}tufts.edu.

Journal of Bacteriology, December 2005, p. 8340-8349, Vol. 187, No. 24
0021-9193/05/$08.00+0     doi:10.1128/JB.187.24.8340-8349.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Yesilkaya, H., Spissu, F., Carvalho, S. M., Terra, V. S., Homer, K. A., Benisty, R., Porat, N., Neves, A. R., Andrew, P. W. (2009). Pyruvate Formate Lyase Is Required for Pneumococcal Fermentative Metabolism and Virulence. Infect. Immun. 77: 5418-5427 [Abstract] [Full Text]  
  • Nobbs, A. H., Lamont, R. J., Jenkinson, H. F. (2009). Streptococcus Adherence and Colonization. Microbiol. Mol. Biol. Rev. 73: 407-450 [Abstract] [Full Text]  
  • Moscoso, M., Garcia, E. (2009). Transcriptional Regulation of the Capsular Polysaccharide Biosynthesis Locus of Streptococcus Pneumoniae: a Bioinformatic Analysis. DNA Res 16: 177-186 [Abstract] [Full Text]  
  • Zeng, L., Burne, R. A. (2009). Transcriptional Regulation of the Cellobiose Operon of Streptococcus mutans. J. Bacteriol. 191: 2153-2162 [Abstract] [Full Text]  
  • Munoz-Elias, E. J., Marcano, J., Camilli, A. (2008). Isolation of Streptococcus pneumoniae Biofilm Mutants and Their Characterization during Nasopharyngeal Colonization. Infect. Immun. 76: 5049-5061 [Abstract] [Full Text]  
  • LeMieux, J., Woody, S., Camilli, A. (2008). Roles of the Sortases of Streptococcus pneumoniae in Assembly of the RlrA Pilus. J. Bacteriol. 190: 6002-6013 [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]  
  • Abranches, J., Nascimento, M. M., Zeng, L., Browngardt, C. M., Wen, Z. T., Rivera, M. F., Burne, R. A. (2008). CcpA Regulates Central Metabolism and Virulence Gene Expression in Streptococcus mutans. J. Bacteriol. 190: 2340-2349 [Abstract] [Full Text]  
  • Shelburne, S. A. III, Keith, D., Horstmann, N., Sumby, P., Davenport, M. T., Graviss, E. A., Brennan, R. G., Musser, J. M. (2008). A direct link between carbohydrate utilization and virulence in the major human pathogen group A Streptococcus. Proc. Natl. Acad. Sci. USA 105: 1698-1703 [Abstract] [Full Text]  
  • Almengor, A. C., Kinkel, T. L., Day, S. J., McIver, K. S. (2007). The Catabolite Control Protein CcpA Binds to Pmga and Influences Expression of the Virulence Regulator Mga in the Group A Streptococcus. J. Bacteriol. 189: 8405-8416 [Abstract] [Full Text]  
  • Kaufman, G. E., Yother, J. (2007). CcpA-Dependent and -Independent Control of Beta-Galactosidase Expression in Streptococcus pneumoniae Occurs via Regulation of an Upstream Phosphotransferase System-Encoding Operon. J. Bacteriol. 189: 5183-5192 [Abstract] [Full Text]  
  • Bizzini, A., Entenza, J. M., Moreillon, P. (2007). Loss of penicillin tolerance by inactivating the carbon catabolite repression determinant CcpA in Streptococcus gordonii. J Antimicrob Chemother 59: 607-615 [Abstract] [Full Text]  
  • McKessar, S. J., Hakenbeck, R. (2007). The Two-Component Regulatory System TCS08 Is Involved in Cellobiose Metabolism of Streptococcus pneumoniae R6. J. Bacteriol. 189: 1342-1350 [Abstract] [Full Text]  
  • Lanie, J. A., Ng, W.-L., Kazmierczak, K. M., Andrzejewski, T. M., Davidsen, T. M., Wayne, K. J., Tettelin, H., Glass, J. I., Winkler, M. E. (2007). Genome Sequence of Avery's Virulent Serotype 2 Strain D39 of Streptococcus pneumoniae and Comparison with That of Unencapsulated Laboratory Strain R6. J. Bacteriol. 189: 38-51 [Abstract] [Full Text]  
  • Deutscher, J., Francke, C., Postma, P. W. (2006). How Phosphotransferase System-Related Protein Phosphorylation Regulates Carbohydrate Metabolism in Bacteria. Microbiol. Mol. Biol. Rev. 70: 939-1031 [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]  


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