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Treponema pallidum Disrupts VE-Cadherin Intercellular Junctions and Traverses Endothelial Barriers Using a

Karen V Lithgow1, Emily Tsao1, Ethan Schovanek1

  • 1Department of Biochemistry and Microbiology, University of Victoria, Victoria, BC, Canada.

Frontiers in Microbiology
|August 6, 2021
PubMed

Insights

Syphilis bacteria (Treponema pallidum) cross endothelial barriers using cholesterol-dependent endocytosis and potentially by disrupting cell junctions. This dual strategy allows bacteria to access underlying tissues without compromising barrier integrity.

Area of Science:

  • Microbiology
  • Cell Biology
  • Infectious Diseases

Background:

  • * *Treponema pallidum* subspecies *pallidum* causes syphilis and must cross the vascular endothelium.
  • * Understanding this traversal mechanism is crucial for developing therapeutic strategies.

Purpose of the Study:

  • * To investigate the mechanisms by which *T. pallidum* traverses endothelial barriers.
  • * To identify specific bacterial factors and host cell interactions involved in endothelial invasion.

Main Methods:

  • * Immunofluorescence microscopy to visualize bacterial localization at endothelial junctions.
  • * Assessment of endothelial barrier permeability.
  • * Use of filipin, a cholesterol-mediated endocytosis inhibitor.

Main Results:

  • * *T. pallidum* localizes to intercellular junctions and disrupts VE-cadherin.
  • * Bacterial traversal occurs without increased endothelial barrier permeability.
  • * Filipin treatment reduces *T. pallidum* endothelial barrier traversal.
  • * A *T. pallidum* vascular adhesin (Tp0751) is implicated in VE-cadherin disruption.

Conclusions:

  • * *T. pallidum* utilizes a cholesterol-dependent, lipid raft-mediated endocytosis pathway for endothelial traversal.
  • * A paracellular route involving intercellular junction disruption may also be employed.
  • * This dual traversal strategy enhances bacterial invasion without compromising barrier function.
Keywords:
Treponema pallidumdisseminationendothelial transmigrationinfectionsyphilis

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