Contributions of the B. burgdorferi Vascular Adhesin BBK32 and Endothelial Surface Receptors to Mechanical Stabilization of Bacterial – Vascular Interactions
Year: 2020
Type: dissertation
Abstract: Systemic 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. Lyme disease is a vector-borne disease caused by the transmission of the bacteria Borrelia burgdorferi through the bite of infected Ixodes scapularis, followed by blood borne dissemination of the bacteria to distal tissue causing arthritis, carditis and neuroborreliosis. We determined that endothelial interactions of B. burgdorferi under physiological shear stress mechanistically resemble selectin-dependent leukocyte rolling. B. burgdorferi 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. Along with BBK32, B. burgdorferi vascular interactions are known to be dependent on plasma fibronectin, glycosaminoglycans, however, the endothelial receptor involved in vascular interactions and dissemination remained unknown. We show that endothelial receptor CD44 which has been previously shown to be involved in leukocyte recruitment and T-cell homing is expressed on the surface of mature endothelial monolayers and are involved in bacterial-endothelial interactions. We have also shown that CD44 is involved in bacterial interactions with the post-capillary venules of mice, and CD44 is important for dissemination of the bacteria out of the bloodstream and into surrounding tissue to cause infection. CD44 is the first endothelial receptor identified to be important for B. burgdorferi vascular adhesion and dissemination. Our 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
Source: TSpace (University of Toronto)
Author: Rhodaba Ebady
Language: English
Subfield: Parasitology
Field: Immunology and Microbiology
Domain: Life Sciences
Open Access status: green
OpenAlex ID: W3154339185