Von Willebrand Factor Mediates Pneumococcal Aggregation and Adhesion in Blood Flow

Area of Science:

• Microbiology
• Hematology
• Vascular Biology

Background:

• Streptococcus pneumoniae causes pneumonia and sepsis, often linked to cardiovascular complications.
• Pneumococci trigger the release of von Willebrand factor (VWF), a key hemostasis glycoprotein.
• Both pneumococcal infections and thromboembolic events involve hemostasis imbalance and elevated VWF.

Purpose of the Study:

• To identify novel interaction partners of Streptococcus pneumoniae.
• To elucidate the role of VWF in pneumococcal adherence and aggregation.
• To characterize the VWF-mediated mechanism of bacterial anchoring in the bloodstream.

Main Methods:

• In vitro infection models using primary endothelial cells.
• Microfluidic systems to simulate shear flow and VWF string formation.
• Immunofluorescence, electron microscopy, and zebrafish infection models.
• Surface plasmon resonance and epitope mapping to identify bacterial binding proteins.

Main Results:

• Von Willebrand factor (VWF) was identified as a novel interaction partner for pneumococci.
• VWF acts as a bridging molecule, mediating heparin-sensitive bacterial adherence to endothelial cells.
• Shear flow induced VWF strings facilitate robust pneumococcal attachment.
• In vivo, VWF recruits to pneumococci, promoting bacterial aggregation within zebrafish vasculature.
• Surface-exposed bacterial enolase was identified as the VWF binding protein, interacting with VWF domain A1.

Conclusions:

• A VWF-mediated mechanism facilitates pneumococcal anchoring in the bloodstream.
• Surface-displayed enolase is crucial for pneumococcal interaction with VWF.
• This interaction promotes intravascular bacterial aggregation, contributing to disease pathogenesis.