Streptolysin O accelerates the conversion of plasminogen to plasmin.

Nat Commun

Division of Infection Medicine, Department of Clinical Sciences Lund, Faculty of Medicine, Lund University, Lund, Sweden.

Published: November 2024

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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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC11589678PMC
http://dx.doi.org/10.1038/s41467-024-54173-6DOI Listing

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