Real-Time High Resolution 3D Imaging of the Lyme Disease Spirochete Adhering to and Escaping from the Vasculature of a Living Host

PLoS Pathogens

Paul Kubes¹  Tara J. Moriarty¹  M. Ursula Norman²  George Chaconas²  Pina Colarusso³  Troy Bankhead³ 

[1] Department of Biochemistry & Molecular Biology, University of Calgary, Calgary, Alberta, Canada;Department of Microbiology & Infectious Diseases, University of Calgary, Calgary, Alberta, Canada;Department of Physiology & Biophysics, University of Calgary, Calgary, Alberta, Canada

关键词: Spirochetes;    Borrelia burgdorferi;    Host-pathogen interactions;    Endothelium;    Blood flow;    Endothelial cells;    Venules;    Bacterial pathogens;   

DOI  :  10.1371/journal.ppat.1000090

学科分类：生物科学（综合）

来源: Public Library of Science

【 摘 要 】

Pathogenic spirochetes are bacteria that cause a number of emerging and re-emerging diseases worldwide, including syphilis, leptospirosis, relapsing fever, and Lyme borreliosis. They navigate efficiently through dense extracellular matrix and cross the blood–brain barrier by unknown mechanisms. Due to their slender morphology, spirochetes are difficult to visualize by standard light microscopy, impeding studies of their behavior in situ. We engineered a fluorescent infectious strain of Borrelia burgdorferi, the Lyme disease pathogen, which expressed green fluorescent protein (GFP). Real-time 3D and 4D quantitative analysis of fluorescent spirochete dissemination from the microvasculature of living mice at high resolution revealed that dissemination was a multi-stage process that included transient tethering-type associations, short-term dragging interactions, and stationary adhesion. Stationary adhesions and extravasating spirochetes were most commonly observed at endothelial junctions, and translational motility of spirochetes appeared to play an integral role in transendothelial migration. To our knowledge, this is the first report of high resolution 3D and 4D visualization of dissemination of a bacterial pathogen in a living mammalian host, and provides the first direct insight into spirochete dissemination in vivo.

【 授权许可】

CC BY