Lyme Disease

Lyme disease is a truly intractable puzzle. Scientists used to consider the tick-borne infection easy to conquer: patients, diagnosed by their bull's-eye rash, could be cured with a weeks-long course of antibiotics. But in recent decades the U.S. Centers for Disease Control and Prevention has realized that up to one in five Lyme patients exhibits persistent debilitating symptoms such as fatigue and pain, known as post-treatment Lyme disease syndrome, and no one understands why. The problem is growing. The incidence of Lyme in the U.S. has increased by about 70 percent over the past decade. Today experts estimate that at least 300,000 people in the U.S. are infected every year; in areas in the Northeast, more than half of adult black-legged ticks carry the Lyme bacterial spirochete, Borrelia burgdorferi. Although the issue is far from settled, new research lends support to the controversial notion that the disease lingers because these bacteria evade antibiotics—and that timing drug treatments differently could eliminate some persistent infections.
These ideas stem from the observation of a few rogue bacterial cells. Kim Lewis, director of the antimicrobial discovery center at Northeastern University, and his colleagues grew B. burgdorferi in the laboratory, treated them with various antibiotics and found that whereas most of the bacteria died within the first day, a small percentage—called persister cells—managed to survive the drug onslaught. Scientists first discovered persister cells in 1944 in Staphylococcus aureus, the agent of staph infections, and Lewis and others have observed them in other species of bacteria, too—but the observations that B. burgdorferi also form persisters is new.
“These are some of the most robust persisters we've seen,” says Lewis, whose results were published online in May in Antimicrobial Agents and Chemotherapy. “Over days, in the presence of antibiotic, their numbers don't decline.” Researchers at Johns Hopkins University similarly identified B. burgdorferi persister cells this past spring.
Persisters are not antibiotic-resistant mutants; they are genetically identical to their vulnerable counterparts. Instead they are bacteria that have gone into a dormant state, ceasing the types of cellular activities that antibiotics typically thwart. Previous research has shown that when persisters of other bacterial species are removed from a bath of antibiotics, they begin to grow again. This fact prompted Lewis and his colleagues to try treating B. burgdorferi with antibiotics in pulsed doses—administering the drugs, stopping and then administering them again—to see if they could kill the persisters once they began to regrow. It worked, which suggests that if persisters are responsible for lasting infections in people, treating patients on and off with antibiotics could help. Lewis and his colleagues, as well as the Johns Hopkins scientists, are also exploring other treatment options, such as different drugs and drug combinations.