Integrin binding by B orrelia burgdorferi P 66 facilitates dissemination but is not required for infectivity

Summary P 66, a B orrelia burgdorferi surface protein with porin and integrin‐binding activities, is essential for murine infection. The role of P 66 integrin‐binding activity in B . burgdorferi infection was investigated and found to affect transendothelial migration. The role of integrin binding, specifically, was tested by mutation of two amino acids ( D 205 A , D 207 A ) or deletion of seven amino acids ( D el202–208). Neither change affected surface localization or channel‐forming activity of P 66, but both significantly reduced binding to α v β 3 . Integrin‐binding deficient B . burgdorferi strains caused disseminated infection in mice at 4 weeks post‐subcutaneous inoculation, but bacterial burdens were significantly reduced in some tissues. Following intravenous inoculation, the D el202–208 bacteria were below the limit of detection in all tissues assessed at 2 weeks post‐inoculation, but bacterial burdens recovered to wild‐type levels at 4 weeks post‐inoculation. The delay in tissue colonization correlated with reduced migration of the D el202–208 strains across microvascular endothelial cells, similar to Δp66 bacteria. These results indicate that integrin binding by P 66 is important to efficient dissemination of B . burgdorferi , which is critical to its ability to cause disease manifestations in incidental hosts and to its maintenance in the enzootic cycle.