Borrelia burgdorferi infection-associated surface proteins ErpP, ErpA, and ErpC bind human plasminogen

Area of Science:

• Microbiology
• Infectious Diseases
• Molecular Biology

Background:

• Borrelia burgdorferi, the causative agent of Lyme disease, utilizes host-derived plasmin for infection.
• Plasminogen-binding proteins on the spirochete surface are crucial for bacterial dissemination.
• Degradation of the extracellular matrix by plasmin aids bacterial spread.

Purpose of the Study:

• To investigate the role of Borrelia burgdorferi outer surface proteins ErpP, ErpA, and ErpC in binding host plasminogen.
• To characterize the binding mechanism of ErpP to plasminogen, focusing on the role of lysine residues.
• To determine if Erp proteins can bind both plasminogen and factor H simultaneously.

Main Methods:

• Characterization of ErpP binding to plasminogen using dose-dependent assays.
• Site-directed mutagenesis of lysine residues in ErpP to assess their role in binding.
• Inhibition assays using epsilon-aminocaproic acid and assessment of ionic interaction effects (NaCl, heparin).
• Investigation of simultaneous binding of plasminogen and factor H to ErpP.

Main Results:

• ErpP, ErpA, and ErpC bind plasminogen in a dose-dependent manner.
• Lysine residues at the carboxy terminus of ErpP are critical for plasminogen binding.
• Binding is independent of ionic interactions.
• Bound plasminogen can be converted to active plasmin.
• Erp proteins bind both plasminogen and factor H concurrently without competition.

Conclusions:

• ErpP, ErpA, and ErpC are key mediators of Borrelia burgdorferi plasminogen binding.
• The interaction involves specific lysine residues on ErpP and targets lysine binding site I of plasminogen.
• These proteins facilitate bacterial dissemination through plasmin generation.
• Erp proteins possess dual-binding capabilities, interacting with both plasminogen and factor H, potentially enhancing immune evasion and dissemination.