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Streptolysin O accelerates the conversion of plasminogen to plasmin

Tang, Di LU orcid ; Khakzad, Hamed ; Hjortswang, Elisabeth LU orcid ; Malmström, Lars LU ; Ekström, Simon LU ; Happonen, Lotta LU and Malmström, Johan LU orcid (2024) In Nature Communications 15. p.1-15
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... (More)
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. (Less)
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author
; ; ; ; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Streptolysins/metabolism, Plasminogen/metabolism, Fibrinolysin/metabolism, Bacterial Proteins/metabolism, Humans, Streptokinase/metabolism, Streptococcus pyogenes/metabolism, Protein Binding, Host-Pathogen Interactions, Tissue Plasminogen Activator/metabolism, Mass Spectrometry, Fibrinolysis
in
Nature Communications
volume
15
article number
10212
pages
15 pages
publisher
Nature Publishing Group
external identifiers
  • scopus:85210176504
  • pmid:39587097
ISSN
2041-1723
DOI
10.1038/s41467-024-54173-6
project
Properties of Protective Antibody Responses against Bacterial Pathogens
language
English
LU publication?
yes
id
ea96afd9-fb3d-4482-b5e0-842d594ff444
date added to LUP
2024-11-25 21:45:36
date last changed
2025-07-10 02:35:49
@article{ea96afd9-fb3d-4482-b5e0-842d594ff444,
  abstract     = {{Group A <i>Streptococcus </i>(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.}},
  author       = {{Tang, Di and Khakzad, Hamed and Hjortswang, Elisabeth and Malmström, Lars and Ekström, Simon and Happonen, Lotta and Malmström, Johan}},
  issn         = {{2041-1723}},
  keywords     = {{Streptolysins/metabolism; Plasminogen/metabolism; Fibrinolysin/metabolism; Bacterial Proteins/metabolism; Humans; Streptokinase/metabolism; Streptococcus pyogenes/metabolism; Protein Binding; Host-Pathogen Interactions; Tissue Plasminogen Activator/metabolism; Mass Spectrometry; Fibrinolysis}},
  language     = {{eng}},
  month        = {{11}},
  pages        = {{1--15}},
  publisher    = {{Nature Publishing Group}},
  series       = {{Nature Communications}},
  title        = {{Streptolysin O accelerates the conversion of plasminogen to plasmin}},
  url          = {{http://dx.doi.org/10.1038/s41467-024-54173-6}},
  doi          = {{10.1038/s41467-024-54173-6}},
  volume       = {{15}},
  year         = {{2024}},
}