How ticks transmit Lyme disease to humans: Imaging technique leads to better understanding

Lyme disease is caused by transmission of the spirochete bacterium Borrelia burgdorferi from ticks to humans but for a number of technical reasons, the transmission process has been difficult to study.

Radolf and researchers Star Dunham-Ems and Melissa Caimano tried a novel approach. They genetically modified a virulent strain of B. burgdorferi to express green fluorescent protein (GFP). "This bacterium glows and can be followed in the living state as it migrates through the tick to the mouse during feeding," explains Radolf. "Then using a powerful microscopic technique called confocal microscopy, we discovered that the transmission process unfolds quite differently than previously believed."

Spirochetes in culture are highly motile, and it is widely believed that during feeding, the spirochetes in the midgut rapidly move through the wall of the midgut. But Radolf and his team found that during much of the feeding period, the spirochetes do not move. They actually divide and surround the cells of the midgut lining or epithelium, forming tight networks. "We also found that the reason they don't move is that the tick midgut secretes molecules that actually inhibit the motility of the spirochetes," explains Radolf.

Eventually, spirochetes in the networks reach the base of the epithelium by completely surrounding the epithelial cells. At this point, they become motile, detach, and completely penetrate the midgut, although in very small numbers. These few bacteria then swim to the salivary glands, which they penetrate en route to the mouse. "So rather than being entirely motility-driven, dissemination of spirochetes within ticks actually happens in two phases," says Radolf, "which is something we didn't know before."

Lyme disease is the most prevalent vector-borne infection in the United States with more than 25,000 new cases reported annually. A substantial percentage of these cases occur in Connecticut. "The improved understanding of the transmission process revealed by our study could lead to novel strategies for controlling the spread of Lyme disease," says Radolf.