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 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 Seidl, K. Articles by Bischoff, M. Search for Related Content PubMed PubMed Citation Articles by Seidl, K. Articles by Bischoff, M.

 Previous Article  |  Next Article 

Antimicrobial Agents and Chemotherapy, April 2006, p. 1183-1194, Vol. 50, No. 4
0066-4804/06/$08.00+0     doi:10.1128/AAC.50.4.1183-1194.2006
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

Staphylococcus aureus CcpA Affects Virulence Determinant Production and Antibiotic Resistance

Kati Seidl,^1, Martin Stucki,^1, Martin Ruegg,¹ Christiane Goerke,² Christiane Wolz,² Llinos Harris,³ Brigitte Berger-Bächi,¹ and Markus Bischoff^1*

Department of Medical Microbiology, University of Zürich, Zürich, Switzerland,¹ Institute for Medical Microbiology and Hygiene, University Hospital Tübingen, Tübingen, Germany,² AO Research Institute, Davos, Switzerland³

Received 27 October 2005/ Returned for modification 11 January 2006/ Accepted 3 February 2006

Carbon catabolite protein A (CcpA) is known to function as a major regulator of gene expression in different gram-positive organisms. Deletion of the ccpA homologue (saCOL1786) in Staphylococcus aureus was found to affect growth, glucose metabolization, and transcription of selected virulence determinants. In liquid culture, deletion of CcpA decreased the growth rate and yield; however, the effect was only transient during the exponential-growth phase as long as glucose was present in the medium. Depletion of glucose and production of lactate was delayed, while the level of excretion of acetate was less affected and was even higher in the mutant culture. On solid medium, in contrast, growth of the ccpA mutant resulted in smaller colonies containing a lower number of CFU per colony. Deletion of CcpA had an effect on the expression of important virulence factors of S. aureus by down-regulating RNAIII, the effector molecule of the agr locus, and altering the transcription patterns of hla, encoding -hemolysin, and spa, encoding protein A. CcpA inactivation markedly reduced the oxacillin resistance levels in the highly methicillin-resistant S. aureus strain COLn and the teicoplanin resistance level in a glycopeptide-intermediate-resistant S. aureus strain. The presence of CcpA in the capsular polysaccharide serotype 5 (CP5)-producing strain Newman abolished capsule formation and decreased cap operon transcription in the presence of glucose. The staphylococcal CcpA thus not only is involved in the regulation of carbon metabolism but seems to function as a modulator of virulence gene expression as well.

K.S. and M.S. contributed equally to the article.

This article has been cited by other articles:

• Seidl, K., Goerke, C., Wolz, C., Mack, D., Berger-Bachi, B., Bischoff, M. (2008). Staphylococcus aureus CcpA Affects Biofilm Formation. Infect. Immun. 76: 2044-2050 [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]  
• Meier, S., Goerke, C., Wolz, C., Seidl, K., Homerova, D., Schulthess, B., Kormanec, J., Berger-Bachi, B., Bischoff, M. (2007). {sigma}B and the {sigma}B-Dependent arlRS and yabJ-spoVG Loci Affect Capsule Formation in Staphylococcus aureus. Infect. Immun. 75: 4562-4571 [Abstract] [Full Text]  
• Makhlin, J., Kofman, T., Borovok, I., Kohler, C., Engelmann, S., Cohen, G., Aharonowitz, Y. (2007). Staphylococcus aureus ArcR Controls Expression of the Arginine Deiminase Operon. J. Bacteriol. 189: 5976-5986 [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]