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. 1992 Jan;60(1):196–201. doi: 10.1128/iai.60.1.196-201.1992

Tissue-type plasminogen activator-mediated activation of plasminogen on the surface of group A, C, and G streptococci.

P Kuusela 1, M Ullberg 1, O Saksela 1, G Kronvall 1
PMCID: PMC257522  PMID: 1370273

Abstract

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.

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Selected References

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  1. Bajaj A. P., Castellino F. J. Activation of human plasminogen by equimolar levels of streptokinase. J Biol Chem. 1977 Jan 25;252(2):492–498. [PubMed] [Google Scholar]
  2. Broder C. C., Lottenberg R., Boyle M. D. Mapping of the human plasmin domain recognized by the unique plasmin receptor of group A streptococci. Infect Immun. 1989 Sep;57(9):2597–2605. doi: 10.1128/iai.57.9.2597-2605.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Broder C. C., Lottenberg R., von Mering G. O., Johnston K. H., Boyle M. D. Isolation of a prokaryotic plasmin receptor. Relationship to a plasminogen activator produced by the same micro-organism. J Biol Chem. 1991 Mar 15;266(8):4922–4928. [PubMed] [Google Scholar]
  4. Broeseker T. A., Boyle M. D., Lottenberg R. Characterization of the interaction of human plasmin with its specific receptor on a group A streptococcus. Microb Pathog. 1988 Jul;5(1):19–27. doi: 10.1016/0882-4010(88)90077-0. [DOI] [PubMed] [Google Scholar]
  5. Danø K., Andreasen P. A., Grøndahl-Hansen J., Kristensen P., Nielsen L. S., Skriver L. Plasminogen activators, tissue degradation, and cancer. Adv Cancer Res. 1985;44:139–266. doi: 10.1016/s0065-230x(08)60028-7. [DOI] [PubMed] [Google Scholar]
  6. Deutsch D. G., Mertz E. T. Plasminogen: purification from human plasma by affinity chromatography. Science. 1970 Dec 4;170(3962):1095–1096. doi: 10.1126/science.170.3962.1095. [DOI] [PubMed] [Google Scholar]
  7. Friberger P., Knös M., Gustavsson S., Aurell L., Claeson G. Methods for determination of plasmin, antiplasmin and plasminogen by means of substrate S-2251. Haemostasis. 1978;7(2-3):138–145. doi: 10.1159/000214252. [DOI] [PubMed] [Google Scholar]
  8. Kuusela P., Saksela O. Binding and activation of plasminogen at the surface of Staphylococcus aureus. Increase in affinity after conversion to the Lys form of the ligand. Eur J Biochem. 1990 Nov 13;193(3):759–765. doi: 10.1111/j.1432-1033.1990.tb19397.x. [DOI] [PubMed] [Google Scholar]
  9. Laemmli U. K. Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature. 1970 Aug 15;227(5259):680–685. doi: 10.1038/227680a0. [DOI] [PubMed] [Google Scholar]
  10. Lottenberg R., Broder C. C., Boyle M. D. Identification of a specific receptor for plasmin on a group A streptococcus. Infect Immun. 1987 Aug;55(8):1914–1918. doi: 10.1128/iai.55.8.1914-1918.1987. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Markus G., Evers J. L., Hobika G. H. Comparison of some properties of native (Glu) and modified (Lys) human plasminogen. J Biol Chem. 1978 Feb 10;253(3):733–739. [PubMed] [Google Scholar]
  12. Parkkinen J., Hacker J., Korhonen T. K. Enhancement of tissue plasminogen activator-catalyzed plasminogen activation by Escherichia coli S fimbriae associated with neonatal septicaemia and meningitis. Thromb Haemost. 1991 May 6;65(5):483–486. [PubMed] [Google Scholar]
  13. Parkkinen J., Korhonen T. K. Binding of plasminogen to Escherichia coli adhesion proteins. FEBS Lett. 1989 Jul 3;250(2):437–440. doi: 10.1016/0014-5793(89)80772-0. [DOI] [PubMed] [Google Scholar]
  14. Reddy K. N., Markus G. Mechanism of activation of human plasminogen by streptokinase. Presence of active center in streptokinase-plasminogen complex. J Biol Chem. 1972 Mar 25;247(6):1683–1691. [PubMed] [Google Scholar]
  15. Saksela O., Rifkin D. B. Cell-associated plasminogen activation: regulation and physiological functions. Annu Rev Cell Biol. 1988;4:93–126. doi: 10.1146/annurev.cb.04.110188.000521. [DOI] [PubMed] [Google Scholar]
  16. Sjöholm I. Studies on the conformational changes of plasminogen induced during activation to plasmin and by 6-aminohexanoic acid. Eur J Biochem. 1973 Nov 15;39(2):471–479. doi: 10.1111/j.1432-1033.1973.tb03146.x. [DOI] [PubMed] [Google Scholar]
  17. Ullberg M., Kronvall G., Karlsson I., Wiman B. Receptors for human plasminogen on gram-negative bacteria. Infect Immun. 1990 Jan;58(1):21–25. doi: 10.1128/iai.58.1.21-25.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Ullberg M., Kronvall G., Wiman B. New receptor for human plasminogen on gram positive cocci. APMIS. 1989 Nov;97(11):996–1002. doi: 10.1111/j.1699-0463.1989.tb00508.x. [DOI] [PubMed] [Google Scholar]

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