Thieving bacteria use hot goods in hideout.

Disease-causing microbes have achieved notoriety for their resourcefulness, often borrowing a molecule from the afflicted host organism to aid infection. The bacterium that produces Lyme disease takes this stratagem a step further. It steals a mammalian host's molecule and uses it to travel within an insect.

The Lyme disease bacterium, Borrelia burgdorferi, spends part of its life cycle in a tick, which then passes the microbe into a mammal. There, the invaders spread through the body, causing flulike symptoms and sometimes more serious illness.

In the past few years, several research groups have shown that B. burgdorferi binds to and activates a mammalian enzyme called plasminogen. In test-tube studies, this enzyme helped the bacterium cross a layer of human cells. These results suggested that B. burgdorferi uses plasminogen to spread within the mammalian host.

A team of microbiologists tested this idea using a genetically engineered mouse that does not make plasminogen. The researchers discovered that, rather than playing a major role in bacterial dissemination within the mouse, the enzyme helps the bacteria break down barriers inside the tick. Jorge L. Benach of the State University of New York at Stony Brook and his colleagues report their findings in the June 27 CELL.

"This is really a landmark paper," says Justin D. Radolf, an infectious disease physician at the University of Texas Southwestern Medical Center at Dallas. "Before this, several groups had shown that these bacteria can acquire plasminogen on their surface, but no one had come up with a way to examine how it fits into the bacterial life cycle."

To infect mammals, the bacteria must travel from a tick's gut, where they live most of the time, to the tick's salivary glands. This journey involves burrowing into the fluid-filled cavity that surrounds the gut, swimming through the fluid, and crossing another layer of tissue into the salivary glands. There the bacteria mix with saliva, which the tick spits into its mammalian host while feeding. Traversing these barriers requires an appropriate tool.

The bacteria acquire such a tool--plasminogen--when the tick gorges itself on the mammal's blood. Benach's team showed that if the tick feasts on plasminogen-deficient mice, most of the B. burgdorferi remain stuck in the insect's gut. Thirty times more bacteria can make it all the way to the salivary glands when the tick has fed on normal mice.

"Having plasminogen greatly facilitates the dissemination of Borrelia through the tick," says Benach. "All of the activity for migration is contributed by the mammalian host."

Somewhat surprisingly, the researchers found that the bacteria do not require mammalian plasminogen to spread within mice. When they inoculated mice with lab-raised B. burgdorferi not previously exposed to plasminogen, the bacteria invaded several organs, regardless of whether the mice made the enzyme. Moreover, when two plasminogen-defective mice were infected by ticks rather than needles, the bacteria spread to their internal organs.

Similar experiments, not yet published, by another research group yielded a different conclusion. When infected ticks fed on plasminogen-deficient mice, B. burgorferi rarely reached the animals' internal organs, says Mark S. Klempner of Tufts University School of Medicine in Boston.

The Benach group's report is the first that "nails down" the role of a mammalian protein in an insect, says microbiologist Kathleen A. McDonough of the New York State Department of Health in Albany. "The bacterium has to deal with the tick as well as the mammal." The researchers used cutting-edge tools to dissect these relationships, which scientists must understand in order to figure out how to block infection, she adds.