Porins from Salmonella typhimurium accelerate human blood coagulation in vitro by selective stimulation of thrombin

B Di Micco1, S Metafora, G Colonna

  • 1Dipartimento di Biochimica e Biofisica Francesco Cedrangolo and Centro di Ricerca Interdipartimentale di Scienze Computazionali e Biotecnologiche, Seconda Università degli Studi di Napoli, Napoli, Italy.

Insights

Salmonella typhimurium porins significantly speed up human blood coagulation by targeting thrombin. This discovery offers insights into Gram-negative septic shock and disseminated intravascular coagulation (DIC).

Area of Science:

  • Microbiology
  • Hematology
  • Biochemistry

Background:

  • Porins are major hydrophobic outer membrane proteins found in Gram-negative bacteria like Salmonella typhimurium.
  • Gram-negative bacterial infections can lead to severe complications such as disseminated intravascular coagulation (DIC) and septic shock.
  • The interaction between bacterial components and human coagulation factors is crucial for understanding pathogenesis.

Purpose of the Study:

  • To investigate the effect of Salmonella typhimurium porins on human blood coagulation.
  • To identify the specific target of porin-induced procoagulant activity.
  • To explore the potential role of porins in the pathogenesis of DIC during Gram-negative septic shock.

Main Methods:

  • Purification of porins from Salmonella typhimurium.
  • In vitro assays to assess the impact of porins on human blood coagulation.
  • Experiments designed to identify the molecular target of porin-mediated coagulation acceleration.

Main Results:

  • Micromolar concentrations of Salmonella typhimurium porins markedly accelerated human blood coagulation in vitro.
  • Data indicated that thrombin is the primary target of the porin-induced procoagulant effect.
  • A potential binding interaction between porins and thrombin was suggested as the mechanism.

Conclusions:

  • Salmonella typhimurium porins possess significant procoagulant activity.
  • Porins accelerate coagulation by interacting with thrombin.
  • These findings have implications for understanding the pathogenesis of DIC in Gram-negative bacterial infections and septic shock.

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