Illuminating the roles of the Borrelia burgdorferi adhesins

Abstract

The Lyme disease spirochetes, Borrelia burgdorferi (sensu lato), must cause persistent, disseminated infection to be maintained in the natural enzootic cycle. In human Lyme disease, spirochetes spread from the site of a tick bite to colonize multiple tissue sites, causing multisystem clinical manifestations. The Lyme spirochetes produce many adhesive surface proteins that collectively recognize diverse host substrates and cell types and are likely to promote dissemination and chronic infection in a variety of tissues. Recent application of state-of-the-art in vivo imaging technologies is illuminating mechanisms of interaction of B. burgdorferi with the host and the importance of multiple adhesins during mammalian infection.

Keywords: Borrelia burgdorferi; Lyme disease; adhesins; dissemination; intravital imaging; transmigration.

Figure 1

The course of Borrelia burgdorferi infection and Lyme disease in humans. Certain strains of laboratory mice also develop arthritis and carditis.

Figure 2

Intravital microscopy (IVM) of GFP-labeled B. burgdorferi in a post-capillary venule of mouse skin. Imaging was performed with a spinning disk laser confocal microscope. The blood vessel (red) was stained with PECAM-1 antibody conjugated to AlexaFluor555. The scale bar is 49 μm. This figure is reproduced from [25].

Figure 3

Summary of the current state of knowledge regarding microvascular interaction and transmigration by B. burgdorferi. This figure is modified from [23] and reproduced with permission from [24].

Figure 4

Two-step model for BBK32-mediated vascular adhesion. The left inset depicts the tethering step mediated by high affinity BBK32–Fn interactions through the Fn-binding domain. The right inset depicts dragging interactions mediated through BBK32–GAG binding sequences. This figure is reproduced with permission from [24].