Streptococcus gallolyticus subsp. gallolyticus endocarditis isolate interferes with coagulation and activates the...

Area of Science:

• Microbiology
• Immunology
• Hematology

Background:

• Streptococcus gallolyticus subsp. gallolyticus (formerly S. bovis biotype I) increasingly causes bacteremia and infective endocarditis, particularly in the elderly.
• The underlying mechanisms of infective endocarditis, involving immune and coagulation systems, remain incompletely understood.

Purpose of the Study:

• To investigate the interaction between Streptococcus gallolyticus subsp. gallolyticus and the human contact system.
• To elucidate the role of this interaction in the physiopathology of S. gallolyticus subsp. gallolyticus infections.

Main Methods:

• Studied the activation of the human contact system by S. gallolyticus subsp. gallolyticus in vitro.
• Assessed the binding and activation of contact factors (e.g., Factor XII) on the bacterial surface.
• Measured bradykinin release and changes in intrinsic coagulation time.
• Investigated the role of the bacterial Pil1 protein using binding assays (K_D determination).

Main Results:

• S. gallolyticus subsp. gallolyticus activates the human contact system.
• This activation leads to high-molecular-weight kininogen (HK) cleavage, releasing pro-inflammatory bradykinin.
• The bacteria initiate the intrinsic pathway of coagulation, prolonging coagulation time.
• Factor XII binds with high affinity (K_D = 13 nM) to the bacterial Pil1 protein.
• Pil1 expression is specific to S. gallolyticus subsp. gallolyticus, suggesting a crucial role in virulence.

Conclusions:

• Streptococcus gallolyticus subsp. gallolyticus directly engages and activates the human contact system.
• The bacterial Pil1 protein is a key virulence factor mediating the activation of Factor XII and subsequent inflammation and coagulation.
• These findings provide new insights into the pathogenesis of S. gallolyticus subsp. gallolyticus-associated diseases.