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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 [vessel exiting] spirochetes were most commonly observed at endothelial junctions [between cells], and translational motility ["runs"] of spirochetes appeared to play an integral role in transendothelial migration [movement across the cell boundary].

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.

Source: PLoS (Public Library of Science) Pathogens, June 2008. 4(6) Moriarty TJ, Norman MU, Colarusso P, Bankead T, Kubes P, Chaconas G. Departments of Biochemistry & Molecular Biology, Microbiology & Infectious Diseases, and Physiology & Biophysics, University of Calgary, Calgary, Alberta, Canada. [E-mail: chaconas@ucalgary.ca]