This Article
Right arrow Full Text
Right arrow Full Text (PDF)
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 Google Scholar
Google Scholar
Right arrow Articles by Bryan, J. D.
Right arrow Articles by Shelver, D. W.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Bryan, J. D.
Right arrow Articles by Shelver, D. W.

 Previous Article  |  Next Article 

Journal of Bacteriology, March 2009, p. 1847-1854, Vol. 191, No. 6
0021-9193/09/$08.00+0     doi:10.1128/JB.01124-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

Streptococcus agalactiae CspA Is a Serine Protease That Inactivates Chemokines {triangledown}

Joshua D. Bryan and Daniel W. Shelver*

Department of Microbiology and Immunology, LSU Health Sciences Center in Shreveport, Shreveport, Louisiana 71130

Received 11 August 2008/ Accepted 23 December 2008

Streptococcus agalactiae (group B Streptococcus [GBS]) remains a leading cause of invasive infections in neonates and has emerged as a pathogen of the immunocompromised and elderly populations. The virulence mechanisms of GBS are relatively understudied and are still poorly understood. Previous evidence indicated that the GBS cspA gene is necessary for full virulence and the cleavage of fibrinogen. The predicted cspA product displays homology to members of the extracellular cell envelope protease family. CXC chemokines, many of which can recruit neutrophils to sites of infection, are important signaling peptides of the immune system. In this study, we purified CspA and demonstrated that it readily cleaved the CXC chemokines GRO-{alpha}, GRO-β, GRO-{gamma}, neutrophil-activating peptide 2 (NAP-2), and granulocyte chemotactic protein 2 (GCP-2) but did not cleave interleukin-8. CspA did not cleave a panel of other test substrates, suggesting that it possesses a certain degree of specificity. CXC chemokines also underwent cleavage by whole GBS cells in a cspA-dependent manner. CspA abolished the abilities of three representative CXC chemokines, GRO-{gamma}, NAP-2, and GCP-2, to attract and activate neutrophils. Genetic and biochemical evidence indicated that CspA is a serine protease with S575 at its active site. D180 was also implicated as part of the signature serine protease catalytic triad, and both S575 and D180 were required for both N-terminal and C-terminal autocatalytic processing of CspA.

* Corresponding author. Mailing address: Department of Microbiology and Immunology, Louisiana State University Health Sciences Center in Shreveport, 1501 Kings Highway, Shreveport, LA 71130. Phone: (318) 675-4884. Fax: (318) 675-5764. E-mail: dshelv{at}lsuhsc.edu

{triangledown} Published ahead of print on 29 December 2008.

Journal of Bacteriology, March 2009, p. 1847-1854, Vol. 191, No. 6
0021-9193/09/$08.00+0     doi:10.1128/JB.01124-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.





Copyright © 2009 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»