Integrin binding by Borrelia burgdorferi P66 facilitates dissemination but is not required for infectivity

Area of Science:

• Microbiology
• Infectious Diseases
• Molecular Biology

Background:

• P66 is a Borrelia burgdorferi surface protein crucial for infection.
• P66 exhibits porin and integrin-binding activities.
• Integrin binding by P66 influences bacterial migration.

Purpose of the Study:

• To investigate the role of P66's integrin-binding activity in Borrelia burgdorferi infection.
• To determine how P66-integrin interactions affect bacterial dissemination and colonization.

Main Methods:

• Mutagenesis of P66 (D205A, D207A) and deletion (Del202-208) to impair integrin binding.
• Assessment of bacterial binding to αvβ3 integrin.
• Murine infection models (subcutaneous and intravenous inoculation) to evaluate dissemination and colonization.
• In vitro transendothelial migration assays.

Main Results:

• P66 mutations/deletions reduced binding to αvβ3 integrin without affecting surface localization or channel activity.
• Integrin-binding deficient B. burgdorferi showed reduced dissemination and delayed tissue colonization in mice.
• Impaired bacterial migration across microvascular endothelial cells was observed for P66 mutants.
• Reduced bacterial burdens were noted in specific tissues following subcutaneous inoculation.

Conclusions:

• P66's integrin-binding activity is vital for efficient Borrelia burgdorferi dissemination.
• This binding facilitates bacterial migration across endothelial cells, crucial for infection establishment.
• Impaired integrin binding by P66 affects the spirochete's ability to cause disease and persist in the enzootic cycle.