Introduction: Treponema pallidum is the causative agent of venereal syphilis, a human-specific sexually transmitted infection characterised by multi-stage disease and diverse clinical manifestations. T. pallidum undergoes rapid hematogenous dissemination, accessing distant organ sites and penetrating tissue, placental, and blood-brain barriers. Tp0751 is an adhesin that interacts with the host vasculature and mediates bacterial adherence to endothelial cells under shear flow conditions. This study explores Tp0751-mediated adhesion to the vascular endothelium.
Methods Tp0751, expressed in a non-infectious model spirochete [Borrelia burgdorferi (Bb-Tp0751)], was assessed for a gain-of-function adhesion phenotype using attachment assays. Interaction specificity was probed with competitive inhibition studies using synthetic peptides of Tp0751 host-binding regions. Affinity chromatography coupled with mass spectrometry was used to identify endothelial receptors for Tp0751. Membrane receptors isolated from human umbilical vein endothelial cells (HUVECs) were incubated with Tp0751-affinity columns and interacting proteins were identified with mass spectrometry.
Results Here we demonstrate that Bb-Tp0751 adheres to HUVECs under stationary conditions. The laminin receptor (LamR) was identified as an endothelial receptor for Tp0751. LamR is a brain endothelial receptor for other neurotropic invasive pathogens, including Neisseria meningitidis. Current investigations will validate the Tp0751-LamR interaction and characterise the functional outcomes of Tp0751 adhesion to endothelial cells.
Conclusion These investigations reveal the mechanics of T. pallium attachment to endothelial cells, the fundamental step in the process of T. pallidum vascular dissemination. A complete understanding of this process will provide opportunities to prevent T. pallidum attachment to the host vasculature to facilitate syphilis vaccine development.
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