This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Supplemental material
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 Sitkiewicz, I.
Right arrow Articles by Musser, J. M.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Sitkiewicz, I.
Right arrow Articles by Musser, J. M.

 Previous Article  |  Next Article 

Infection and Immunity, February 2006, p. 1339-1351, Vol. 74, No. 2
0019-9567/06/$08.00+0     doi:10.1128/IAI.74.2.1339-1351.2006
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

Expression Microarray and Mouse Virulence Analysis of Four Conserved Two-Component Gene Regulatory Systems in Group A Streptococcus {dagger}

Izabela Sitkiewicz1,2 and James M. Musser1,2*

Center for Human Bacterial Pathogenesis Research, Department of Pathology, Baylor College of Medicine, Houston, Texas 77030,1 Center for Molecular and Translational Human Infectious Diseases Research, The Methodist Hospital Research Institute, and Department of Pathology, The Methodist Hospital, Houston, Texas 770302

Received 1 November 2005/ Accepted 18 November 2005

Group A streptococcus (GAS) is a gram-positive human bacterial pathogen that causes diseases ranging from relatively mild epithelial cell surface infections to life-threatening invasive episodes. Much is known about the extracellular molecules that contribute to host-pathogen interactions, but in contrast, far less information is available about regulatory genes that control the expression of individual or multiple GAS virulence factors. The eight GAS genomes that have been sequenced have 12 conserved two-component gene regulatory systems (TCSs), but only 3 of these 12 have been studied in detail. Using an allelic replacement strategy with a nonpolar cassette, we inactivated the response regulator of four TCSs that have only weak homology with TCS genes of known or inferred function in other bacteria. The mutant strains were analyzed by expression microarray analysis at four time points and tested in two mouse infection models. Each TCS influenced expression (directly or indirectly) of 12 to 41% of all chromosomal genes, as assessed by growth in Todd-Hewitt broth and a custom Affymetrix GeneChip. None of the isogenic mutant strains was significantly altered for mouse virulence based on intraperitoneal inoculation. Similarly, compared to the wild-type strain, there was no significant difference in skin lesion size for three of the four mutants. In contrast, the {Delta}M5005_Spy_0680 mutant strain produced significantly larger abscesses after subcutaneous inoculation into mice, consistent with a hypervirulence phenotype. The mutant strain had significantly higher in vitro expression of several proven and putative virulence genes, including scpA, encoding a peptidase that inactivates complement protein C5a. Together, the data provide new information about previously uncharacterized GAS TCSs.

* Corresponding author. Mailing address: Center for Molecular and Translational Human Infectious Diseases Research, The Methodist Hospital Research Institute, Department of Pathology, F-816, Houston, TX 77030. Phone: (713) 441-0164. Fax: (713) 790-6460. E-mail: jmmusser{at}tmh.tmc.edu.

Editor: D. L. Burns

{dagger} Supplemental material for this article may be found at http://iai.asm.org/.

Infection and Immunity, February 2006, p. 1339-1351, Vol. 74, No. 2
0019-9567/06/$08.00+0     doi:10.1128/IAI.74.2.1339-1351.2006
Copyright © 2006, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Trevino, J., Perez, N., Ramirez-Pena, E., Liu, Z., Shelburne, S. A. III, Musser, J. M., Sumby, P. (2009). CovS Simultaneously Activates and Inhibits the CovR-Mediated Repression of Distinct Subsets of Group A Streptococcus Virulence Factor-Encoding Genes. Infect. Immun. 77: 3141-3149 [Abstract] [Full Text]  
  • Leday, T. V., Gold, K. M., Kinkel, T. L., Roberts, S. A., Scott, J. R., McIver, K. S. (2008). TrxR, a New CovR-Repressed Response Regulator That Activates the Mga Virulence Regulon in Group A Streptococcus. Infect. Immun. 76: 4659-4668 [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]  
  • 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]  
  • Kreikemeyer, B., Nakata, M., Koller, T., Hildisch, H., Kourakos, V., Standar, K., Kawabata, S., Glocker, M. O., Podbielski, A. (2007). The Streptococcus pyogenes Serotype M49 Nra-Ralp3 Transcriptional Regulatory Network and Its Control of Virulence Factor Expression from the Novel eno ralp3 epf sagA Pathogenicity Region. Infect. Immun. 75: 5698-5710 [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»