Streptolysin O accelerates the conversion of plasminogen to plasmin - Archive ouverte HAL
Article Dans Une Revue Nature Communications Année : 2024

Streptolysin O accelerates the conversion of plasminogen to plasmin

Di Tang
Lars Malmström
Simon Ekström
Lotta Happonen
Johan Malmström

Résumé

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
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hal-04804299 , version 1 (26-11-2024)

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Di Tang, Hamed Khakzad, Elisabeth Hjortswang, Lars Malmström, Simon Ekström, et al.. Streptolysin O accelerates the conversion of plasminogen to plasmin. Nature Communications, 2024, 15, ⟨10.1038/s41467-024-54173-6⟩. ⟨hal-04804299⟩
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