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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.



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