Streptolysin O accelerates the conversion of plasminogen to plasmin

Di Tang (), Hamed Khakzad, Elisabeth Hjortswang, Lars Malmström, Simon Ekström, Lotta Happonen and Johan Malmström ()
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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

Nature Communications, 2024, vol. 15, issue 1, 1-15

Abstract: 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.

Date: 2024
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DOI: 10.1038/s41467-024-54173-6

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