Tissue-type plasminogen activator-mediated activation of plasminogen on the surface of group A, C, and G streptococci.
The interaction of Glu-plasminogen with group A, C, and G streptococci and subsequent formation of surface-associated plasminogen by tissue-type plasminogen activator (t-PA) were studied. Binding of 125I-Glu-plasminogen to streptococci greatly facilitated its activation to 125I-Glu-plasmin by exogenous t-PA, whereas activation in the absence of bacteria took place only slowly. Glu-plasmin formed on the streptococcal surface was further converted to the Lys form. Similar activation and modification took place also in the presence of plasminogen-depleted plasma, containing functional t-PA and plasmin inhibitors, indicating that the surface-associated enzymes were protected against these inhibitors. Lys-plasminogen was 10- to 30-fold more potent than Glu-plasminogen or Glu-plasmin in inhibiting the binding of 125I-Glu-plasminogen to streptococci. This indicated a higher affinity of the Lys form towards plasminogen-binding molecule(s) on the streptococcal surface. The surface-associated plasmin was also enzymically active as judged by digestion of chromogenic substrate S-2251. Surface-associated plasmin activity was observed only when the incubations were carried out in the presence of t-PA and Glu-plasminogen or human plasma as the source of plasminogen. Under these conditions, soluble enzymatic activity was also recovered in the supernatant of group A streptococci. This favors the idea that plasmin can be released from the bacterial surface. The findings provide a mechanism for streptococci to adopt proteolytic activity by binding a host-derived enzyme zymogen on their surface, where the subsequent activation then takes place. The results suggest a role for surface-associated plasmin activity in tissue tropism and tissue invasiveness of streptococci.
Kuusela
P
P
Department of Bacteriology and Immunology, University of Helsinki, Finland.
Ullberg
M
M
Saksela
O
O
Kronvall
G
G
D007611:Aprotinin / Q000494:pharmacology; D004591:Electrophoresis, Polyacrylamide Gel; D005341:Fibrinolysin / Q000096:biosynthesis*; D006801:Humans; D066298:In Vitro Techniques; D010958:Plasminogen / Q000378:metabolism*; D015849:Plasminogen Inactivators / Q000494:pharmacology; D013291:Streptococcus / Q000378:metabolism*; D010959:Tissue Plasminogen Activator / Q000502:physiology*
D015849:Plasminogen Inactivators; D010958:Plasminogen; D007611:Aprotinin; D010959:Tissue Plasminogen Activator; D005341:Fibrinolysin