Structural bionanomechanical view at bacterial dissemination

The Lyme disease spirochete Borrelia burgdorferi is transmitted through the Ixodes ticks to the dermis of a mammalian host. Further dissemination to distal tissues occurs by hematogenous and non-hematogenous routes. The detailed mechanisms of dissemination and invasion are not well understood. Our team recently showed that borrelial adhesins DbpA/B and BBK32 significantly enhance the borrelial motility in the extracellular matrix and support the acquisition of the spirochetes by ticks. Now, we focus on the mechanism of borrelia transendothelial migration. To address this, we plan to use advanced electron microscop y and atomic force microscopy techniques and characterize the integrity, biomechanical properties, and distribution of junction proteins of the endothelial cells during B. burgdorferi transmigration. Identification of the mechanisms and molecules involved in endothelial transmigration is essential in understanding the pathogenesis of Lyme disease. We will image the penetration of Borrelia through endothelial cells in 3D and high resolution and assess biomechanical parameters and structural changes of endothelial monolayer during/after bacterial transmigration .