Bacteria-released outer membrane vesicles promote disseminated intravascular coagulation

Area of Science:

• Microbiology
• Immunology
• Pathogenesis

Background:

• Sepsis often leads to disseminated intravascular coagulation (DIC), increasing patient mortality.
• The precise mechanisms by which bacteria induce DIC remain incompletely understood.
• Outer membrane vesicles (OMVs) are bacterial microvesicles implicated in pathogenesis.

Purpose of the Study:

• To investigate the role of bacterial outer membrane vesicles (OMVs) in the development of sepsis-induced disseminated intravascular coagulation (DIC).

Main Methods:

• Mice were injected with purified Escherichia coli (E.coli) OMVs or E.coli strains with altered OMV production.
• Toll-like receptor 4 (TLR4) knock-out mice were used to assess receptor dependency.
• DIC development was evaluated through coagulopathy, thrombi formation, organ injury, and mortality.

Main Results:

• E.coli OMVs induced coagulopathy, thrombi deposition, organ injury, and mortality in a TLR4-dependent manner.
• Genetic deletion of the ypjA gene, crucial for OMV production, significantly reduced E.coli-induced DIC and mortality.
• Purified OMVs alone were sufficient to trigger DIC development.

Conclusions:

• Bacterial OMVs play a significant role in the pathogenesis of DIC during Gram-negative bacterial infections.
• Targeting bacterial OMV production presents a potential therapeutic strategy to prevent infection-associated coagulopathy.