Enhancement of tissue plasminogen activator-catalyzed plasminogen activation by Escherichia coli S fimbriae associated with neonatal septicaemia and meningitis.
The effect of Escherichia coli strains isolated from blood and cerebrospinal fluid of septic infants on plasminogen activation was studied. These strains typically carry a filamentous surface protein, S fimbria, that has formerly been shown to bind to endothelial cells and interact with plasminogen. The bacteria effectively promoted plasminogen activation by tissue plasminogen activator (t-PA) which was inhibited by epsilon-aminocaproic acid. A recombinant strain expressing S fimbriae accelerated t-PA-catalyzed plasminogen activation to a similar extent as did the wild-type strains whereas the nonfimbriate recipient strain had no effect. After incubation with t-PA and plasminogen, the S-fimbriate strain displayed bacterium-bound plasmin activity whereas the nonfimbriate strain did not. Bacterium-associated plasmin generation was also observed with a strain expressing mutagenized S fimbriae that lack the cell-binding subunit SfaS but not with a strain lacking the major subunit SfaA. Both t-PA and plasminogen bound to purified S fimbriae in a lysine-dependent manner and purified S fimbriae accelerated t-PA-catalyzed plasminogen activation. The results indicate that E. coli S fimbriae form a complex with t-PA and plasminogen which enhances the rate of plasminogen activation and generates bacterium-bound plasmin. This may promote bacterial invasion and persistence in tissues and contribute to the systemic activation of fibrinolysis in septicaemia.
Parkkinen
J
J
Department of Medical Chemistry, University of Helsinki, Finland.
Hacker
J
J
Korhonen
T K
TK
D000595:Amino Acid Sequence; D002384:Catalysis; D004926:Escherichia coli / Q000302:isolation & purification / Q000502:physiology*; D004927:Escherichia coli Infections / Q000382:microbiology; D010861:Fimbriae, Bacterial / Q000502:physiology*; D006801:Humans; D007231:Infant, Newborn; D008581:Meningitis / Q000382:microbiology*; D008969:Molecular Sequence Data; D010958:Plasminogen / Q000378:metabolism*; D018805:Sepsis / Q000382:microbiology*; D010959:Tissue Plasminogen Activator / Q000378:metabolism*
D010958:Plasminogen; D010959:Tissue Plasminogen Activator