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

被引:98
作者
Bergmann, S
Rohde, M
Preissner, KT
Hammerschmidt, S
机构
[1] Univ Wurzburg, Res Ctr Infect Dis, D-97070 Wurzburg, Germany
[2] Univ Giessen, Inst Biochem, Giessen, Germany
[3] German Res Ctr Biotechnol, GBF, Braunschweig, Germany
关键词
pneumococci; plasmin activity; enolase; fibrinolysis; degradation;
D O I
10.1160/TH05-05-0369
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
The glycolytic enzyme alpha-enolase represents one of the non-classical 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) tissue-type 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.
引用
收藏
页码:304 / 311
页数:8
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