This Article Full Text (PDF) Other Versions of this Article: JB.00917-07v1 190/2/590    most recent 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 Reprints and Permissions Copyright Information Books from ASM Press MicrobeWorld Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Hendriksen, W. T. Articles by Hermans, P. W.M. Search for Related Content PubMed PubMed Citation Articles by Hendriksen, W. T. Articles by Hermans, P. W.M.

 Previous Article  |  Next Article 

J. Bacteriol. doi:10.1128/JB.00917-07
Copyright (c) 2007, American Society for Microbiology and/or the Listed Authors/Institutions. All Rights Reserved.

CodY of Streptococcus pneumoniae: link between nutritional gene regulation and colonization

Department of Pediatrics, Erasmus MC-Sophia Children's Hospital, 3000 DR Rotterdam, The Netherlands; Laboratory of Pediatric Infectious Diseases, Radboud University Nijmegen Medical Centre, 6500 HB Nijmegen, The Netherlands; Department of Molecular Genetics, University of Groningen, Groningen Biomolecular Sciences and Biotechnology institute, PO Box 14, 9750 AA Haren, The Netherlands

^* To whom correspondence should be addressed. Email: P.Hermans{at}cukz.umcn.nl.

	Abstract

CodY is a nutritional regulator mainly involved in amino acid metabolism. It has been extensively studied in Bacillis subtilis and Lactococcus lactis. We investigated the role of CodY in gene regulation and virulence of the human pathogen Streptococcus pneumoniae. We constructed a codY-mutant and examined the effect on gene and protein expression by microarray and 2D DIGE analysis. The pneumococcal CodY-regulon was found to consist predominantly of genes involved in amino acid metabolism, but also several other cellular processes, such as carbon metabolism and iron uptake. By means of electrophoretic mobility shift assays and DNA footprinting, we showed that most targets identified are under direct control of CodY. By mutating DNA predicted to represent the CodY-box based on the L. lactis consensus, we demonstrated that this sequence is indeed required for in vitro DNA-binding to target promoters. Similar to L. lactis, DNA-binding of CodY was enhanced in the presence of branched chain amino acids, but not by GTP. We observed in experimental mouse models that codY is transcribed in the murine nasopharynx and lungs, and is specifically required for colonization. This finding was underscored by the diminished ability of the codY-mutant to adhere to nasopharyngeal cells in vitro. Furthermore, we found that pcpA, activated by CodY, is required for adherence to nasopharyngeal cells, suggesting a direct link between nutritional regulation and adherence. In conclusion, pneumococcal CodY predominantly regulates genes involved in amino acid metabolism and contributes to the early stages of infection, i.e. colonization of the nasopharynx.

This article has been cited by other articles:

• Kloosterman, T. G., Witwicki, R. M., van der Kooi-Pol, M. M., Bijlsma, J. J. E., Kuipers, O. P. (2008). Opposite Effects of Mn2+ and Zn2+ on PsaR-Mediated Expression of the Virulence Genes pcpA, prtA, and psaBCA of Streptococcus pneumoniae. J. Bacteriol. 190: 5382-5393 [Abstract] [Full Text]  
• Lemos, J. A., Nascimento, M. M., Lin, V. K., Abranches, J., Burne, R. A. (2008). Global Regulation by (p)ppGpp and CodY in Streptococcus mutans. J. Bacteriol. 190: 5291-5299 [Abstract] [Full Text]  
• Glover, D. T., Hollingshead, S. K., Briles, D. E. (2008). Streptococcus pneumoniae Surface Protein PcpA Elicits Protection against Lung Infection and Fatal Sepsis. Infect. Immun. 76: 2767-2776 [Abstract] [Full Text]  
• Hendriksen, W. T., Kloosterman, T. G., Bootsma, H. J., Estevao, S., de Groot, R., Kuipers, O. P., Hermans, P. W. M. (2008). Site-Specific Contributions of Glutamine-Dependent Regulator GlnR and GlnR-Regulated Genes to Virulence of Streptococcus pneumoniae. Infect. Immun. 76: 1230-1238 [Abstract] [Full Text]