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Streptolysin O accelerates the conversion of plasminogen to plasmin

Author

Listed:
  • Di Tang

    (Lund University)

  • Hamed Khakzad

    (Université de Lorraine, CNRS, Inria, LORIA)

  • Elisabeth Hjortswang

    (Lund University)

  • Lars Malmström

    (Lund University)

  • Simon Ekström

    (Lund University)

  • Lotta Happonen

    (Lund University)

  • Johan Malmström

    (Lund University
    Lund University)

Abstract

Group A Streptococcus (GAS) is a human-specific bacterial pathogen that can exploit the plasminogen-plasmin fibrinolysis system to dismantle blood clots and facilitate its spread and survival within the human host. In this study, we use affinity-enrichment mass spectrometry to decipher the host-pathogen protein-protein interaction between plasminogen and streptolysin O, a key cytolytic toxin produced by GAS. This interaction accelerates the conversion of plasminogen to plasmin by both the host tissue-type plasminogen activator and streptokinase, a bacterial plasminogen activator secreted by GAS. Integrative structural mass spectrometry analysis shows that the interaction induces local conformational shifts in plasminogen. These changes lead to the formation of a stabilised intermediate plasminogen-streptolysin O complex that becomes significantly more susceptible to proteolytic processing by plasminogen activators. Our findings reveal a conserved and moonlighting pathomechanistic function for streptolysin O that extends beyond its well-characterised cytolytic activity.

Suggested Citation

  • Di Tang & Hamed Khakzad & Elisabeth Hjortswang & Lars Malmström & Simon Ekström & Lotta Happonen & Johan Malmström, 2024. "Streptolysin O accelerates the conversion of plasminogen to plasmin," Nature Communications, Nature, vol. 15(1), pages 1-15, December.
    • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-54173-6
    DOI: 10.1038/s41467-024-54173-6
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