Lyme disease bacteria insights may lead to more effective prevention

Spirochete Under Microscope New findings about the bacterium that causes Lyme disease could lead to new strategies to reduce infections and resulting chronic illness, according to research published in mBio, the online open-access journal of the American Society for Microbiology.

Lyme disease is an infectious disease caused by a spirochete (spiral shaped bacterium) known as Borrelia burgdorferi and is most commonly spread by ticks. Despite the infectious agent and mode of transmission being known for over three decades the cases of Lyme disease are continuing to climb. The highest rates are seen in the Northeastern United States but many people from different regions and countries also suffer from the disease.

The most obvious sign of initial Lyme disease infection is a chracteristic rash around a tick bite known as Erythema migrans, or a "bullseye" rash, so named because it is circular and red around the outside with a pale centre. Symptoms of the disease are multiple, ranging from fatigue, weakness and headache, to cognitive, mood, and neurological disorders. The large number and systemic nature of symptoms has contributed to controversy. Some experts say Lyme disease is acute and easily treated with a relatively short course of antibiotics, while others suggest a chronic form may develop. Certainly there are no shortage of individuals who suffer chronic symptoms following Lyme infection - many become severely debilitated, losing jobs and relationships.

Researchers looked at the immune system of the white-footed mouse, a very common reservoir for Borrelia burgdorferi (along with deer and other wildlife), finding that it responds differently to different strains of the bacterium. This insight will help scientists tweak the animals' immune response to prevent infection. A vaccine that keeps these wild mice free of the pathogen could significantly reduce the spread of the disease from mice to ticks to humans.

"There's no human vaccine, and there's not likely to be one," says Alan Barbour of the University of California, Irvine, the lead author of the study. "We have to focus on lowering the risk. One way to do that is by treating the animals that carry the disease." Rabies offers a good example of how this might be accomplished, says Barbour. By deploying vaccine-laced food bait, public health officials have managed to lower the rabies infection rate in wildlife and significantly limited the spread of the disease to pets and humans.

Although Lyme disease only emerged in the U.S. in the past 40 years or so, around 25,000 cases are now reported every year in this country (with many more going undiagnosed and reported) and the medical costs of these cases are estimated to range in the billions of dollars. Those who go on to develop chronic Lyme disease often find themselves spending a fortune of their own money desperately trying to recover their health since a lack of recognition means insurance doesn't cover the costs.

Despite the growing importance of the disease, little is known about the evolution and ecology of the bacterium that causes the illness.Barbour and his colleagues sought to understand why as many as 15 different strains of B. burgdorferi exist in the wild at differing degrees of prevalence. In the parts of the country where Lyme disease is most common, the majority of white-footed mice are infected with B. burgdorferi during the course of the year. Unlike humans and lab mice, white-footed mice don't get sick when they're infected so the bacteria grow and multiply within them, and when a deer tick bites it ingests the bacteria along with the animals blood.

Investigators at UC Irvine exposed white-footed mice to various strains of B. burgdorferi in the lab and tracked the course of the infection. All the B. burgdorferi strains infected the white-footed mice, but some strains managed to grow to high densities in various mouse tissues while others did not.

Barbour says the immune reactions the mice mounted against the various strains explain these discrepancies: the greater the immune response, the fewer bacteria found in a mouse's tissues and vice-versa. Importantly, the strains that grew to greatest densities within the mice are also the strains that are most prevalent in the wild.

When they looked at the immune reaction to individual B. burgdorferi proteins the authors found a complex interplay of reactivities. The mice reacted in different degrees to the various proteins present in a single bacterial strain, which could explain why such a great diversity of B. burgdorferi strains are sustained in the wild, according to the researchers.

Barbour says knowing more about how the white-footed mouse reacts to all the various B. burgdorferi strains and immunogenic proteins will help vaccine developers select the best proteins to put in a vaccine. "The best candidate for the mouse vaccine is something that's the same in all the [B. burgdorferi] strains," he says.

Once a vaccine for the white-footed mouse is developed, it will need to be tested by exposing immunized mice to a selected set of diverse B. burgdorferi strains, says Barbour, and the results of this study can help make that selection. "If we can find five that are representative, that would be an advantage."

This study, he says, "is going to provide a foundation for future studies in understanding the infection in these animals as we proceed with developing vaccines."

It seems this new approach to prevention may soon help to curb the ever increasing rates of Lyme disease in humans. Whether vaccines can be developed for other animal carriers of B. burgdorferi such as deer is not discussed by Barbour and colleagues but would seem a logical extension of this work - and if possible, reduce infection of humans even further.

Reference:

Baum E Hue F and Barbour AG (2012) Experimental infections of the reservoir species Peromyscus leucopus with diverse strains of Borrelia burgdorferi, a Lyme disease agent mBio 3(6):e00434-12