title: 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.
abstract: The glycolytic enzyme alpha-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) 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.
authors.affiliation: Research Center for Infectious Diseases, University of Würzburg, Germany.
authors.forename: Simone
authors.initials: S
authors.lastname: Bergmann
authors.forename: Manfred
authors.initials: M
authors.lastname: Rohde
authors.forename: Klaus T
authors.initials: KT
authors.lastname: Preissner
authors.forename: Sven
authors.initials: S
authors.lastname: Hammerschmidt
mesh_terms: D020816:Amino Acid Motifs; D001665:Binding Sites; D045744:Cell Line, Tumor; D002462:Cell Membrane / Q000378:metabolism; D003094:Collagen / Q000737:chemistry; D004338:Drug Combinations; D005109:Extracellular Matrix / Q000378:metabolism*; D005337:Fibrin / Q000737:chemistry*; D005340:Fibrinogen / Q000737:chemistry; D006019:Glycolysis; D006801:Humans; D007797:Laminin / Q000737:chemistry; D008855:Microscopy, Electron, Scanning; D009068:Movement; D009154:Mutation; D010751:Phosphopyruvate Hydratase / Q000737:chemistry*; D010958:Plasminogen / Q000737:chemistry*; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D011509:Proteoglycans / Q000737:chemistry; D013296:Streptococcus pneumoniae / Q000201:enzymology* / Q000378:metabolism*
chemical_list: D004338:Drug Combinations; D007797:Laminin; D011509:Proteoglycans; C059485:matrigel; D005337:Fibrin; D005340:Fibrinogen; D010958:Plasminogen; D003094:Collagen; D010751:Phosphopyruvate Hydratase