Circulating bacterial membrane vesicles cause sepsis in rats.

Area of Science:

• Microbiology
• Immunology
• Pathophysiology

Background:

• Gram-negative bacteria are a primary cause of sepsis, a leading global cause of death.
• Inflammation can persist even after bacteremia is cleared, suggesting other factors contribute to sepsis progression.
• Bacterial outer membrane vesicles (OMVs) contain lipopolysaccharide (LPS) and proteins, potentially mediating inflammatory responses.

Purpose of the Study:

• To investigate whether bacterial outer membrane vesicles (OMVs) can initiate an inflammatory response independently of the parent bacteria.
• To characterize the physiological, histological, and molecular effects of OMVs in a sepsis model.

Main Methods:

• Outer membrane vesicles (OMVs) were isolated from Escherichia coli cultures.
• LPS concentration in OMVs was quantified.
• Adult male Sprague-Dawley rats were administered OMVs, lipopolysaccharide (LPS), lactated Ringer's, or sham treatment.

Main Results:

• OMV infusion induced sepsis-consistent physiological changes, including altered heart rate and mean arterial pressure.
• Pro-inflammatory cytokines (tumor necrosis factor α, interleukin 6) were elevated in OMV-treated rats.
• Neutrophil recruitment and vascular adhesion molecule expression increased in OMV-exposed animals, though less than with soluble LPS.

Conclusions:

• Bacterial outer membrane vesicles (OMVs) can independently initiate inflammatory responses contributing to sepsis.
• While soluble LPS elicits a stronger response, OMVs induce significant inflammatory effects exceeding those of lactated Ringer's.
• Further research is needed to fully elucidate the complex biomolecular interactions of OMVs in sepsis.