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Tang D, Khakzad H, Hjortswang E, Malmström L, Ekström S, Happonen L, Malmström J
Nat Commun 15 (1) 10212 [2024-11-25; online 2024-11-25]
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.
Structural Proteomics [Technology development]
PubMed 39587097
DOI 10.1038/s41467-024-54173-6
Crossref 10.1038/s41467-024-54173-6
pii: 10.1038/s41467-024-54173-6
pmc: PMC11589678