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Updated: Jul 11, 2026
Humanized Mouse Model to Study Bacterial Infections Targeting the Microvasculature
Published on: April 1, 2014
Interaction with human plasminogen system turns on proteolytic activity in Streptococcus agalactiae and enhances its
Vanessa Magalhães1, Isabel Veiga-Malta, Maria Rosário Almeida
1ICBAS- Instituto de Ciências Biomédicas de Abel Salazar, Porto, Portugal.
Abstract:
Interactions of several microbial pathogens with the plasminogen system increase their invasive potential. In this study, we show that Streptococcus agalactiae binds human plasminogen which can be subsequently activated to plasmin, thus generating a proteolytic bacterium. S. agalactiae binds plasminogen via the direct pathway, using plasminogen receptors, and via the indirect pathway through fibrinogen receptors. The glyceraldehyde-3-phosphate dehydrogenase is one of the S. agalactiae proteins that bind plasminogen. Presence of exogenous activators such as uPA and tPA are required to activate bound plasminogen. Results from competitive inhibition assays indicate that binding is partially mediated through the lysine binding sites of plasminogen. Following plasminogen binding and activation, S. agalactiae is able to degrade in vitro fibronectin, one of the host extracellular matrix proteins. Moreover, incubation of S. agalactiae with either plasminogen alone, or plasminogen plus fibrinogen, in the presence of tPA enhanced its virulence in C57BL/6 mice, suggesting that acquisition of plasmin-like activity by the bacteria increase their invasiveness.
Insights
Streptococcus agalactiae binds and activates human plasminogen to plasmin, enhancing bacterial virulence. This proteolytic activity aids in degrading host fibronectin and increasing invasiveness in mice.
Area of Science:
- Microbiology
- Molecular Biology
- Pathogenesis
Background:
- Microbial pathogens often exploit host systems to increase invasiveness.
- The plasminogen system is a key target for pathogen invasion strategies.
Purpose of the Study:
- To investigate the interaction between Streptococcus agalactiae and the human plasminogen system.
- To determine if this interaction enhances bacterial virulence and invasiveness.
Main Methods:
- Assessing Streptococcus agalactiae binding to human plasminogen via direct and indirect pathways.
- Identifying specific bacterial proteins involved in plasminogen binding, such as glyceraldehyde-3-phosphate dehydrogenase.
- Evaluating the activation of bound plasminogen to plasmin using exogenous activators (uPA, tPA).
- Conducting competitive inhibition assays to understand binding mechanisms.
- Measuring the degradation of fibronectin by bacteria-bound plasmin.
- Assessing bacterial virulence in a mouse model (C57BL/6) after incubation with plasminogen and activators.
Main Results:
- Streptococcus agalactiae directly binds human plasminogen through specific receptors and indirectly via fibrinogen receptors.
- Glyceraldehyde-3-phosphate dehydrogenase was identified as a plasminogen-binding protein.
- Bound plasminogen requires exogenous activators like tPA for conversion to active plasmin.
- Binding involves plasminogen's lysine binding sites.
- Activated plasmin degrades host fibronectin in vitro.
- Exposure to plasminogen and tPA significantly enhanced S. agalactiae virulence in a mouse model.
Conclusions:
- Streptococcus agalactiae effectively utilizes the human plasminogen system, generating a proteolytic bacterium.
- Acquisition of plasmin-like activity by S. agalactiae increases its invasiveness and virulence.
- Targeting this interaction could be a strategy to combat S. agalactiae infections.
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