Biomechanics of Borrelia burgdorferi Vascular Interactions

Abstract

SUMMARYSystemic dissemination of microbes is critical for progression of many infectious diseases and is associated with most mortality due to bacterial infection. The physical mechanisms mediating a key dissemination step, bacterial association with vascular endothelia in blood vessels, remain unknown. Here, we show that endothelial interactions of the Lyme disease spirochete Borrelia burgdorferi under physiological shear stress mechanistically resemble selectin-dependent leukocyte rolling. Specifically, these interactions are mediated by transfer of mechanical load along a series of adhesion complexes and are stabilized by tethers and catch bond properties of the bacterial adhesin BBK32. Furthermore, we found that the forces imposed on adhesive bonds under flow may be small enough to permit active migration driven by bacterial flagellar motors. These findings provide insight into the biomechanics of bacterial-vascular interactions and demonstrate that disseminating bacteria and circulating host immune cells share widely conserved mechanisms for interacting with endothelia under physiological shear stress.

Plasma fibronectin stabilizes Borrelia burgdorferi –endothelial interactions under vascular shear stress by a catch-bond mechanism

“…Therefore, Fn has the potential to support vascular interactions of disseminating pathogens. Consistent with this hypothesis, B. burgdorferi interacts with postcapillary venules (PCVs) in vivo by an Fn-dependent mechanism (7,18,19), and polymorphisms in an S. aureus adhesion protein (adhesin) that strengthen Fn binding are associated with infection of cardiac devices by these bacteria (20). Fn-binding sequences of the surface-localized B. burgdorferi vascular adhesin BBK32 are also important for PCV interactions of this pathogen (19).…”

“…This flow chamber system recapitulates the major qualitative and quantitative properties of B. burgdorferi interactions with dermal PCVs in live mice (7), where the two major types of mobile B. burgdorferi-vascular interactions, tethering and dragging, are Fn-dependent (18,33). Tethering and dragging are distinct initiation steps in the multistep B. burgdorferi-vascular interaction cascade and permit bacteria to slow down sufficiently to extravasate from blood vessels during dissemination (7,18,19,33) (Fig. 1A).…”

“…1A). Tethering bacteria are stabilized by tethers anchoring bacteria to endothelia, move at least 50% more slowly under flow than control beads but faster than 100 μm·s −1 , and pause briefly and repeatedly as they move over endothelial surfaces (7,33) (Fig. 1A).…”

“…1A). Dragging bacteria are not stabilized by tethers, and move more slowly than 100 μm·s −1 (7,33) (Fig. 1A).…”

“…However, many bacteria, including spirochetes, do not form pili or fimbriae. We recently found that endothelial interactions of the Lyme disease spirochete Borrelia burgdorferi under physiological shear stress bear a remarkable biomechanical resemblance to the mechanisms supporting leukocyte rolling on the same surfaces and are stabilized by catch bonds and tethers, even though leukocytes and B. burgdorferi are genetically, morphologically, and physiologically distinct cells (7). Other bacterial pathogens also exploit or mimic strategies used by circulating host cells to adhere to and bypass endothelial barriers under vascular shear stress.…”