By mapping the genetic code of particularly virulent strains of Lyme disease bacteria, scientists may have gotten a step closer to figuring out why symptoms persist for months, or even years, in some people.
Samples from hundreds of patients revealed that certain strains of the Lyme bacteria, Borrelia burgdorferi, have a protective outer layer that contains more of a type of protein that appears to function as armor against the human immune system, giving it a better chance of spreading throughout the body, according to a new study published Thursday in PLOS Pathogens.
“The reason we did this study was to see whether different strains predisposed a patient to a different severity of Lyme disease,” said Dr. Jacob Lemieux, an infectious disease physician at the Massachusetts General Hospital and an assistant professor at the Harvard Medical School. “We also wanted to know what it was about those strains that was linked to an invasive infection.”
The researchers hoped to learn how certain strains of the Lyme bacteria were able to spread beyond the initial bite site, potentially making post-treatment Lyme disease syndrome — when someone experiences lingering symptoms — more likely.
A map of virulent strains’ genes could potentially lead to better therapies, experts said.
“The more we know about how it causes disease, the better we can treat and prevent it,” said Dr. Paul Mead, an epidemiologist at the Centers for Disease Control and Prevention.
Nearly half a million people are infected with the Lyme bacteria each year, according to the CDC. It’s the most common vector-borne disease in the U.S. Others include West Nile virus and Dengue fever, which are spread by mosquitoes, or tick-borne illnesses like Rocky Mountain spotted fever.
Lyme disease symptoms
It’s important to understand why Lyme infections can lead to such disparate outcomes, Mead said.
Symptoms can include:
- Skin rash
- Swollen lymph nodes
- Some facial paralysis
"Some get a more severe form of the illness, such as inflammation in the heart or the membranes around the brain,” Mead said.
It's been challenging to get a deeper understanding of the genetic makeup of Borrelia burgdorferi strains because the bacteria can be detected in the skin and other parts of the body for just a short time. In addition, tests for Lyme generally look only for antibodies, not the actual bacteria.
For the new study, the researchers combined information from four research groups that had collected actual bacterial samples from 299 patients. If a particular patient had bacteria only in a single rash— the hallmark bull’s eye — the infection was considered to be localized.
If the patient had multiple skin rashes, neurological symptoms, or the bacteria were found in blood or spinal fluid samples, the infection was deemed to be disseminated, meaning it had spread beyond the site of the original bite and the rash it caused —potentially raising the risk of lingering Lyme symptoms. Other research has found a higher rate of long Lyme among patients who have disseminated disease early on.
It's unknown how many strains of the Lyme bacteria there are. Environmental pressures keep the bacteria mutating, Lemieux said.
There has been evidence that the strain of bacteria could make a difference in how sick patients become. An earlier study linked infections with a certain strain, OspC type A, with greater inflammation and more severe disease.
Lemieux and his colleagues don’t know exactly which bits of DNA are linked with disease severity. But they think that genes coding for an abundance of certain particles, called lipoproteins, on the surface of the bacteria may be key because they form part of the bacteria’s armor.
Still, it’s likely that the particular strains of Borrelia burgdorferi included in the research aren’t the only factor leading to long Lyme in some people, Lemieux said.
“We do know, for example, that there’s a strong human genetic predisposition for developing post-infection arthritis,” he added.
The possible contribution of human genetics was highlighted in a recent study published in the CDC’s Emerging Infectious Diseases Journal. Researchers found that an immune system marker, a protein called interferon-alpha, is elevated in people with lingering Lyme symptoms, even those who received treatment early.
That protein tells the body’s immune cells to seek and destroy invading microbes. High levels of the protein can lead the immune system to overreact, which can cause pain, swelling and fatigue, some of the very symptoms common to patients with long Lyme.
The new research is at a very early stage, but it is an important step to understanding and treating the disease, said Kim Lewis, a Lyme expert and a professor of biology at Northeastern University in Boston.
For most patients, taking the antibiotic doxycycline can treat symptoms of Lyme.
"What’s scary, and a cause for concern, is that about 10% of those who are treated early, six months later have unresolved symptoms,” Lewis said.
Lewis commended the researchers for taking on the very large task of sequencing bacteria gathered from hundreds of patients.
“They confirmed that a particular type of Borrelia burgdorferi is more disseminating,” said Lewis, who was not involved with the new study. “And that is one that is unfortunately pretty predominant in the Northeast.”
The new study “is well designed and rigorous,” said Armin Alaedini, a Lyme disease researcher and immunologist at Columbia University in New York. “It really confirms and extends earlier work showing that certain specific genotypes are associated with specific manifestations of the disease.”
Longer term, “it’s tempting to speculate that there are specific strains that are associated with a greater risk of developing post-treatment Lyme disease syndrome,” Alaedini said.
He called it a "big step forward" but said a large study that follows people over time is needed to know which patients go on to develop post-treatment Lyme disease syndrome.
“If we could identify a specific gene or gene product that is somehow central to causing inflammation of the heart we might be able to come up with a drug that blocks the effect or an antibody or a vaccine that would target it,” the CDC's Mead said. “But that’s a long way off.”