AUTHOR=Lithgow Karen V. , Tsao Emily , Schovanek Ethan , Gomez Alloysius , Swayne Leigh Anne , Cameron Caroline E. 

TITLE=Treponema pallidum Disrupts VE-Cadherin Intercellular Junctions and Traverses Endothelial Barriers Using a Cholesterol-Dependent Mechanism

JOURNAL=Frontiers in Microbiology

VOLUME=12

YEAR=2021

URL=https://www.frontiersin.org/journals/microbiology/articles/10.3389/fmicb.2021.691731

DOI=10.3389/fmicb.2021.691731

ISSN=1664-302X

ABSTRACT=<p><italic>Treponema pallidum</italic> subspecies <italic>pallidum</italic>, the causative agent of syphilis, traverses the vascular endothelium to gain access to underlying tissue sites. Herein, we investigate the mechanisms associated with <italic>T. pallidum</italic> traversal of endothelial barriers. Immunofluorescence microscopy reveals that a subpopulation of <italic>T. pallidum</italic> localizes to intercellular junctions and that viable <italic>T. pallidum</italic>, as well as a <italic>T. pallidum</italic> vascular adhesin (Tp0751), disrupts the architecture of the main endothelial junctional protein VE-cadherin. Intriguingly, in this study we show that <italic>T. pallidum</italic> traverses endothelial barriers with no disruption in barrier permeability. Furthermore, barrier traversal by <italic>T. pallidum</italic> is reduced by pretreatment of endothelial cells with filipin, an inhibitor that blocks cholesterol-mediated endocytosis. Collectively, these results suggest that <italic>T. pallidum</italic> can use a cholesterol-dependent, lipid raft-mediated endocytosis mechanism to traverse endothelial barriers. Further, treponemal localization to, and disruption of, intercellular junctions suggests that a paracellular route may also be utilized, a dual traversal strategy that has also been observed to occur for leukocytes and other invasive bacteria.</p>