M protein, a classical bacterial virulence determinant, forms complexes with fibrinogen that induce vascular leakage

Area of Science:

• Microbiology
• Immunology
• Pathology

Background:

• Vascular permeability is crucial in inflammation and severe infections.
• Streptococcus pyogenes causes toxic shock syndrome (STSS) with plasma leakage and organ failure.

Purpose of the Study:

• To elucidate the mechanism by which Streptococcus pyogenes M protein contributes to vascular leakage and STSS.

Main Methods:

• Investigated M protein-fibrinogen complex formation and its interaction with neutrophil beta2 integrins.
• Assessed the role of heparin binding protein in vascular leakage.
• Utilized mouse models of M protein injection and S. pyogenes infection.
• Examined tissue biopsies from a patient with necrotizing fasciitis and STSS.

Main Results:

• M protein forms complexes with fibrinogen, activating neutrophils.
• Activated neutrophils release heparin binding protein, inducing vascular leakage.
• M protein or S. pyogenes infection caused pulmonary damage in mice, preventable by a beta2 integrin antagonist.
• M protein/fibrinogen complexes were found in patient biopsies.

Conclusions:

• M protein-fibrinogen complexes are key mediators of vascular leakage in severe S. pyogenes infections.
• Neutrophil activation via beta2 integrins is critical for this pathogenic process.
• Targeting this pathway offers a potential therapeutic strategy for STSS.