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- Naudin, Clément, et al.
(författare)
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Active but inoperable thrombin is accumulated in a plasma protein layer surrounding Streptococcus pyogenes.
- 2015
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Ingår i: Thrombosis and Haemostasis. - 0340-6245. ; 114:4, s. 717-726
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Tidskriftsartikel (refereegranskat)abstract
- Activation of thrombin is a critical determinant in many physiological and pathological processes including haemostasis and inflammation. Under physiological conditions many of these functions are involved in wound healing or eradication of an invading pathogen. However, when activated systemically, thrombin can contribute to severe and life-threatening conditions by causing complications such as multiple multi-organ failure and disseminated intravascular coagulation. In the present study we investigated how the activity of thrombin is modulated when it is bound to the surface of Streptococcus pyogenes. Our data show that S. pyogenes bacteria become covered with a proteinaceous layer when incubated with human plasma, and that thrombin is a constituent of this layer. Though the coagulation factor is found attached to the bacteria with a functional active site, thrombin has lost its capacity to interact with its natural substrates and inhibitors. Thus, the interaction of bacteria with human plasma renders thrombin completely inoperable at the streptococcal surface. This could represent a host defense mechanism to avoid systemic activation of coagulation which could be otherwise induced when bacteria enter the circulation and cause systemic infection.
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| 2. |
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| 3. |
- van Os, G M A, et al.
(författare)
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Induction of Auto-Antibodies Against β(2) -Glycoprotein I in Mice by Protein H of Streptococcus Pyogenes.
- 2011
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Ingår i: Journal of Thrombosis and Haemostasis. - : Elsevier BV. - 1538-7933 .- 1538-7836. ; 9:12, s. 2447-2456
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Tidskriftsartikel (refereegranskat)abstract
- Background: The antiphospholipid syndrome (APS) is characterized by the persistent presence of auto-antibodies against β(2) -Glycoprotein I (β(2) -GPI). β(2) -GPI can exist in two conformations. In plasma it is a circular protein, whereas it adopts a fish-hook shape after binding to phospholipids. Only the latter conformation is recognized by patient antibodies. β(2) -GPI has been shown to interact with Streptococcus pyogenes. Objective: Here we evaluated the potential of S. pyogenes derived proteins to induce auto-antibodies against β(2) -GPI. Methods and results: Four S. pyogenes surface proteins (M1 protein, protein H, SclA and SclB) were found to interact with β(2) -GPI. Only binding to protein H induces a conformational change in β(2) -GPI, thereby exposing a cryptic epitope for APS-related auto-antibodies. Mice were injected with the four proteins. Only mice injected with protein H developed antibodies against the patient antibody related epitope in domain I of β(2) -GPI. Patients with pharyngotonsillitis caused by S. pyogenes who developed antibodies towards protein H also generated anti-β(2) -GPI antibodies. Conclusion: Our study demonstrated that a bacterial protein can induce a conformational change in β(2) -GPI resulting in the formation of auto-antibodies against β(2) -GPI. This constitutes a novel mechanism for the formation of auto-antibodies against β(2) -GPI.
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