The CXC chemokine-degrading protease SpyCep of Streptococcus pyogenes promotes its uptake into endothelial cells.
Cast your vote
You can rate an item by clicking the amount of stars they wish to award to this item.
When enough users have cast their vote on this item, the average rating will also be shown.
Your vote was cast
Thank you for your feedback
Thank you for your feedback
AuthorsKaur, Simran Jeet
Chhatwal, Gursharan S
Talay, Susanne R
MetadataShow full item record
AbstractStreptococcus pyogenes expresses the LPXTG motif-containing cell envelope serine protease SpyCep (also called ScpC, PrtS) that degrades and inactivates the major chemoattractant interleukin 8 (IL-8), thereby impairing host neutrophil recruitment. In this study, we identified a novel function of SpyCep: the ability to mediate uptake into primary human endothelial cells. SpyCep triggered its uptake into endothelial cells but not into human epithelial cells originating from pharynx or lung, indicating an endothelial cell-specific uptake mechanism. SpyCep mediated cellular invasion by an endosomal/lysosomal pathway distinct from the caveolae-mediated invasion pathway of S. pyogenes. Recombinant expression and purification of proteolytically active SpyCep and a series of subfragments allowed functional dissection of the domains responsible for endothelial cell invasion and IL-8 degradation. The N-terminal PR domain was sufficient to mediate endothelial cell invasion, whereas for IL-8-degrading activity, the protease domain and the flanking A domain were required. A polyclonal rabbit serum raised against the recombinant protease efficiently blocked the invasion-mediating activity of SpyCep but not its proteolytic function, further indicating that SpyCep-mediated internalization is independent from its enzymatic activity. SpyCep may thus specifically mediate its own uptake as secreted protein into human endothelial cells.
CitationThe CXC chemokine-degrading protease SpyCep of Streptococcus pyogenes promotes its uptake into endothelial cells. 2010, 285 (36):27798-805 J. Biol. Chem.
AffiliationDepartment of Microbial Pathogenesis, Helmholtz Centre for Infection Research, Inhoffenstrasse 7, D-38124 Braunschweig, Germany.
The following license files are associated with this item:
- The IL-8 protease SpyCEP/ScpC of group A Streptococcus promotes resistance to neutrophil killing.
- Authors: Zinkernagel AS, Timmer AM, Pence MA, Locke JB, Buchanan JT, Turner CE, Mishalian I, Sriskandan S, Hanski E, Nizet V
- Issue date: 2008 Aug 14
- Chemokine-cleaving Streptococcus pyogenes protease SpyCEP is necessary and sufficient for bacterial dissemination within soft tissues and the respiratory tract.
- Authors: Kurupati P, Turner CE, Tziona I, Lawrenson RA, Alam FM, Nohadani M, Stamp GW, Zinkernagel AS, Nizet V, Edwards RJ, Sriskandan S
- Issue date: 2010 Jun
- A chemokine-degrading extracellular protease made by group A Streptococcus alters pathogenesis by enhancing evasion of the innate immune response.
- Authors: Sumby P, Zhang S, Whitney AR, Falugi F, Grandi G, Graviss EA, Deleo FR, Musser JM
- Issue date: 2008 Mar
- Emerging role of the interleukin-8 cleaving enzyme SpyCEP in clinical Streptococcus pyogenes infection.
- Authors: Turner CE, Kurupati P, Jones MD, Edwards RJ, Sriskandan S
- Issue date: 2009 Aug 15
- Cloning, expression, purification, crystallization and preliminary X-ray diffraction analysis of SpyCEP, a candidate antigen for a vaccine against Streptococcus pyogenes.
- Authors: Abate F, Malito E, Falugi F, Margarit Y Ros I, Bottomley MJ
- Issue date: 2013 Oct