The CXC chemokine-degrading protease SpyCep of Streptococcus pyogenes promotes its uptake into endothelial cells.
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Authors
Kaur, Simran JeetNerlich, Andreas
Bergmann, Simone
Rohde, Manfred
Fulde, Marcus
Zähner, Dorothea
Hanski, Emanuel
Zinkernagel, Annelies
Nizet, Victor
Chhatwal, Gursharan S
Talay, Susanne R
Issue Date
2010-09-03
Metadata
Show full item recordAbstract
Streptococcus 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.Citation
The CXC chemokine-degrading protease SpyCep of Streptococcus pyogenes promotes its uptake into endothelial cells. 2010, 285 (36):27798-805 J. Biol. Chem.Affiliation
Department of Microbial Pathogenesis, Helmholtz Centre for Infection Research, Inhoffenstrasse 7, D-38124 Braunschweig, Germany.PubMed ID
20562101Type
ArticleLanguage
enISSN
1083-351Xae974a485f413a2113503eed53cd6c53
10.1074/jbc.M109.098053
Scopus Count
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