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

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

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 -glucosidase, raffinose-inducible -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.

This article has been cited by other articles:

• 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]