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Updated: Jun 27, 2026
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Implementation of a Permeable Membrane Insert-based Infection System to Study the Effects of Secreted Bacterial Toxins on Mammalian Host Cells
Published on: August 19, 2016
Reduced thrombin generation increases host susceptibility to group A streptococcal infection
Hongmin Sun1, Xixi Wang, Jay L Degen
1Department of Internal Medicine, University of Missouri-Columbia, USA.
Blood
|December 6, 2008
Summary
Host hemostatic factors, like fibrinogen and factor V, are crucial for combating bacterial infections. Impaired clotting increases mortality, suggesting thrombosis limits pathogen spread and influences infectious disease susceptibility.
Area of Science:
- Microbiology
- Immunology
- Hematology
Background:
- Bacterial pathogens utilize host plasmin to enhance virulence.
- Group A Streptococcus (GAS) employs streptokinase to activate human plasminogen (PLG).
- The role of thrombin generation in antimicrobial defense requires further investigation.
Purpose of the Study:
- To investigate the role of thrombin generation in antimicrobial host defense against GAS.
- To determine the impact of factor V (FV) and fibrinogen deficiency on GAS infection outcomes.
- To assess the influence of the FV Leiden mutation on GAS infection survival.
Main Methods:
- GAS infection challenge in mice with plasma or platelet FV deficiency.
- Evaluation of mortality rates in F5-deficient and wild-type mice.
- Assessment of GAS infection outcomes in fibrinogen-deficient mice.
- Analysis of survival in GAS-infected mice carrying the FV Leiden mutation.
Main Results:
- FV deficiency in plasma or platelets significantly increased mortality following GAS infection.
- Platelet FV pool plays a critical, previously unappreciated role in host defense.
- Complete fibrinogen deficiency also led to markedly increased mortality.
- The FV Leiden mutation did not confer a survival advantage in GAS-infected mice.
Conclusions:
- Local thrombosis and fibrin deposition are hypothesized to limit pathogen survival and dissemination.
- Variations in human hemostatic factors may influence susceptibility to infectious diseases.
- Thrombin generation is a vital component of the host's antimicrobial defense system.
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