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Mouse skin passage of Streptococcus pyogenes results in increased streptokinase expression and activity
Myrna S Rezcallah1, Michael D P Boyle2, Darren D Sledjeski3
1Department of Microbiology, University of Minnesota Medical School, Minneapolis, MN 55455, USA.
Abstract:
The plasminogen activator streptokinase has been proposed to be a key component of a complex mechanism that promotes skin invasion by Streptococcus pyogenes. This study was designed to compare ska gene message and protein levels in wild-type M1 serotype isolate 1881 and a more invasive variant recovered from the spleen of a lethally infected mouse. M1 isolates selected for invasiveness demonstrated enhanced levels of active plasminogen activator activity in culture. This effect was due to a combination of increased expression of the ska gene and decreased expression of the speB gene. The speB gene product, SpeB, was found to efficiently degrade streptokinase in vitro.
Insights
Streptococcus pyogenes uses streptokinase (ska) to invade skin. More invasive strains show higher ska gene expression and lower SpeB protease activity, which degrades streptokinase.
Area of Science:
- Microbiology
- Molecular Biology
- Infectious Diseases
Background:
- Streptococcus pyogenes causes skin infections.
- The plasminogen activator streptokinase (ska) is implicated in S. pyogenes skin invasion.
- A more invasive M1 serotype variant was identified.
Purpose of the Study:
- Compare ska gene and protein levels in wild-type and invasive S. pyogenes M1 isolates.
- Investigate the role of SpeB in streptokinase regulation.
Main Methods:
- Quantitative analysis of ska gene message and protein.
- Assay of plasminogen activator activity.
- In vitro degradation assays of streptokinase by SpeB.
Main Results:
- Invasive M1 isolates exhibited increased plasminogen activator activity.
- This was linked to higher ska gene expression.
- Invasive isolates showed decreased speB gene expression.
- SpeB efficiently degraded streptokinase in vitro.
Conclusions:
- Increased ska expression and reduced SpeB activity contribute to enhanced S. pyogenes invasiveness.
- SpeB protease activity is a key regulator of streptokinase during infection.
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