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The nine residue plasminogen-binding motif of the pneumococcal enolase is the major cofactor of plasmin-mediated degradation of extracellular matrix, dissolution of fibrin and transmigration

Journal: Thrombosis and Haemostasis
ISSN: 0340-6245
Topic:

Vascular Endothelium and Infectious Diseases

DOI: http://dx.doi.org/10.1160/TH05-05-0369
Issue: 2005: 94/2 (Aug) pp. 233-468
Pages: 304-311

The nine residue plasminogen-binding motif of the pneumococcal enolase is the major cofactor of plasmin-mediated degradation of extracellular matrix, dissolution of fibrin and transmigration

Simone Bergmann 1, Manfred Rohde 2, Klaus T. Preissner 3, Sven Hammerschmidt1*

1Research Center for Infectious Diseases, University of Würzburg, Würzburg, 2 GBF-German Research Centre for Biotechnology, Braunschweig, 3 Institute for Biochemistry, Justus-Liebig-University, Giessen, Germany

Summary

The glycolytic enzyme a-enolase represents one of the nonclassical cell surface plasminogen-binding proteins of Streptococcus pneumoniae. In this study we investigated the impact of an internal plasminogen-binding motif of enolase on degradation of extracellular matrix and pneumococcal transmigration. In the presence of host-derived plasminogen activators (PA) tissuetype PA or urokinase PA and plasminogen S. pneumoniae expressing wild-type enolase efficiently degraded Matrigel or extracellular matrix (ECM). In contrast, amino acid substitutions in the nine residue plasminogen-binding motif of enolase significantly reduced degradation of ECM or Matrigel by mutated pneumococci. Similarly, recombinant wild-type enolase but not a mutated enolase derivative that lacks plasminogen-binding activity efficiently degraded ECM and Matrigel, respectively. In particular, bacterial cell enolase-bound plasmin potentiated dissolution of fibrin or laminin and transmigration of pneumococci through a fibrin matrix. In conclusion, these results provide evidence that the enolase is the major plasminogen-binding protein of pneumococci and that the nine residue plasminogen-binding motif of enolase is the key cofactor for plasmin-mediated pneumococcal degradation and transmigration through host ECM.