Vascular binding of a pathogen under shear force through mechanistically distinct sequential interactions with host...

Area of Science:

• Microbiology
• Pathogen Dissemination
• Infectious Diseases

Background:

• Systemic dissemination of microbial pathogens leads to secondary infections and mortality.
• Borrelia burgdorferi dissemination is critical for Lyme disease progression, but mechanisms remain unclear.
• Bacterial adhesion to vascular surfaces under blood flow shear forces is a key dissemination step.

Purpose of the Study:

• To investigate the in vivo mechanisms of Borrelia burgdorferi BBK32-mediated vascular adhesion.
• To elucidate the roles of host fibronectin (Fn) and glycosaminoglycans (GAGs) in BBK32-dependent adhesion.

Main Methods:

• Real-time microscopic imaging of Borrelia burgdorferi in living mice.
• Analysis of BBK32 interactions with host fibronectin and glycosaminoglycans.

Main Results:

• BBK32-fibronectin interactions act as a molecular brake, enabling bacterial tethering to vascular surfaces.
• BBK32-glycosaminoglycan interactions facilitate bacterial dragging along the vascular surface, forming stable adhesion.
• This two-step mechanism (tethering then dragging) is essential for Borrelia burgdorferi vascular adhesion in vivo.

Conclusions:

• The BBK32 protein mediates bacterial vascular adhesion through a novel tethering-dragging mechanism.
• Understanding this mechanism is vital for controlling Borrelia burgdorferi dissemination.
• Similar mechanisms may be involved in the dissemination of other bacterial pathogens expressing BBK32-like proteins.