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Surface bound plasmin promotes migration of Streptococcus pneumoniae through reconstituted basement membranes
T Eberhard1, G Kronvall, M Ullberg
1Division of Clinical Microbiology, Karolinska Hospital, Stockholm, Sweden.
Abstract:
Penetration of basement membrane is believed to be an essential step in the pathogenesis of bacterial meningitis. Consequently Streptococcus pneumoniae strains were tested for their ability to adhere to reconstituted basement membrane (Matrigel) and in a proceeding step penetrate this membrane by the use of surface activated plasmin. A majority of S. pneumoniae strains tested were found to adhere to reconstituted basement membrane as well as to the purified laminin component. Three out of seventeen strains also adhered to the collagen IV component. All the investigated strains also demonstrated a capacity to bind plasminogen with up to 42,000 plasminogen binding sites per bacterium as estimated by Scatchard analysis. Two strains selected for optimal adhesion and plasminogen binding were further tested for basement membrane penetration using a dual chamber model. Our data show that penetration was achieved within 3-4 h in the presence of plasminogen whereas without plasminogen no strain was able to penetrate during a 21 h incubation. The results suggest a potential role of surface associated plasminogen in bacterial penetration of basement membranes and extracellular matrix.
Insights
Streptococcus pneumoniae uses plasminogen to penetrate basement membranes, a key step in bacterial meningitis pathogenesis. This adhesion and penetration mechanism is crucial for understanding how these bacteria cause infection.
Area of Science:
- Microbiology
- Pathogenesis
- Biochemistry
Background:
- Basement membrane penetration is vital for bacterial meningitis development.
- Streptococcus pneumoniae is a primary cause of bacterial meningitis.
Purpose of the Study:
- To investigate Streptococcus pneumoniae's ability to adhere to and penetrate basement membranes.
- To explore the role of plasminogen in this process.
Main Methods:
- Testing S. pneumoniae strain adherence to Matrigel and laminin.
- Quantifying plasminogen binding sites using Scatchard analysis.
- Assessing basement membrane penetration in a dual chamber model with and without plasminogen.
Main Results:
- Most S. pneumoniae strains adhered to basement membrane components like laminin and collagen IV.
- All tested strains bound significant amounts of plasminogen.
- Penetration occurred within 3-4 hours only in the presence of plasminogen, not in its absence over 21 hours.
Conclusions:
- Surface-associated plasminogen facilitates Streptococcus pneumoniae penetration of basement membranes.
- This mechanism is a potential virulence factor in bacterial meningitis.