Transendothelial migration of the Lyme disease spirochete involves spirochete internalization as an intermediate step...

Area of Science:

• Microbiology
• Cell Biology
• Pathogenesis

Background:

• Lyme borreliosis, caused by Borrelia burgdorferi, is the most common tick-borne illness in the Northern Hemisphere.
• The hematogenous dissemination of Borrelia burgdorferi is crucial for its pathogenesis but remains poorly understood.
• Understanding the mechanisms of Borrelia burgdorferi vascular escape is vital for explaining its diverse clinical manifestations.

Purpose of the Study:

• To elucidate the molecular mechanisms of Borrelia burgdorferi transendothelial migration.
• To identify host cell proteins involved in the dissemination of Borrelia burgdorferi.
• To establish a novel in vitro system for studying Borrelia burgdorferi transmigration.

Main Methods:

• Utilized cultured human microvascular endothelial cells and Borrelia burgdorferi in a specialized medium.
• Observed spirochete transmigration using microscopy and quantified using inhibitors of endocytic pathways and host proteins.
• Investigated the role of Cdc42 and Rac1 in Borrelia burgdorferi internalization and transmigration.

Main Results:

• Borrelia burgdorferi primarily utilizes a transcellular pathway, crossing through endothelial cells rather than exploiting cell junctions.
• Spirochete internalization by endothelial cells is an intermediate step in the transmigration process.
• Host proteins Cdc42 and Rac1 are essential for Borrelia burgdorferi transmigration, with Cdc42 mediating internalization and Rac1 facilitating cellular egress.

Conclusions:

• Borrelia burgdorferi employs a transcellular route for dissemination across endothelial cell monolayers.
• Cdc42 and Rac1 are the first identified host proteins critical for Borrelia burgdorferi transmigration.
• The developed experimental system offers a valuable platform for future research into Borrelia burgdorferi dissemination.