Scientists Have Identified the Lyme Disease Genes Responsible for Severe Symptoms

Scientists Have Identified the Lyme Disease Genes Responsible for Severe Symptoms

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Publish Date:
2 September, 2023
Category:
Mental Health
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Lyme disease was first identified in 1975, in Lyme, Conn., but scientists still have more questions than answers about how the bacteria responsible for the condition that wreaks such havoc for some people, leaving them with debilitating symptoms for years, while causing relatively mild disease for others. Tests for Lyme have high false negative rates, especially early in the infection, so even detecting the disease is challenging.

In a paper published in PLOS Pathogens, an international group of researchers report on the most comprehensive analysis of the Borrelia burgdorferi genome to date, which provides clues about what’s causing more severe forms of the disease, and lays the foundation for developing better diagnostic tests and treatments. The data come from samples painstakingly taken from 299 Lyme patients in the northeastern and midwestern U.S., and central Europe, mostly extracted from skin biopsies of the bullseye-shaped rashes that are a hallmark early sign of infection. The scientists first isolated the bacteria from the biopsied skin samples, then correlated genetic signatures of the bacteria with the patients’ health outcomes. That allowed them to identify genes that were associated with more severe symptoms as well as understand why U.S. patients tend to have different symptoms than those in Europe.

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“This information is foundational for developing diagnostics, vaccines, and therapies,” says Pardis Sabeti, from the Broad Institute of MIT and Harvard, Massachusetts General Hospital, and Harvard University, and a senior author of the paper. “Knowing the genes that are there, we can start seeing the diversity that exists, and characterizing their function. It’s like the Human Genome Project—this genetic information is what’s needed before we can even begin to develop better diagnostics and treatments.”

In the paper, the scientists confirmed previous, smaller genetic studies of B. burgdorferi that correlated genetic markers on the bacterial genome to disease symptoms in people. They found specific genetic changes associated with more severe disease, which could in the future be used to determine whether a particular infection involves a strain of the bacteria that is likely to lead to more serious illness.

They also found specific proteins on the surface of the bacteria that were associated with the ability to spread beyond the initial site of infection (i.e. a tick bite) via the blood to affect other tissues and organs. “That’s when most of the problematic aspects of Lyme disease begins,” says Dr. Jacob Lemieux, from Massachusetts General Hospital and the Broad Institute of MIT and Harvard, and first author of the study. “The bacteria may go to the nervous system, causing neurological Lyme disease, or if it goes to the joints, it can cause Lyme arthritis. Dissemination is a watershed event because it could mean the difference between a mild and severe case.”

Whether these markers are also associated with post Lyme disease syndrome, in which people continue to experience lingering symptoms months or years after their infection, isn’t clear yet. But it could help to demystify what’s causing the syndrome. “Patients who have disseminated Lyme disease do have higher rates of post Lyme disease syndrome,” says Lemieux. “We hypothesize that certain strains of Lyme are more likely to lead to post-treatment Lyme syndrome, and we’d like to identify what those strains are. So knowing which patients are infected with strains that are more likely to disseminate could help us to study new therapeutics and interventions for post Lyme syndrome.”

Read more: How Climate Change Affects the Spread of Lyme Disease

By highlighting possible genetic markers associated with the bacteria’s ability to roam the body after infection, the scientists hope to catalyze additional research into testing and responding to these markers to reduce serious symptoms.

The extensive genetic information gathered in this study also provides clues about why people in the U.S. experience different Lyme symptoms than those in Europe, and why tests in the U.S. may not detect infections picked up overseas. “We found that the genetics [of the bacterial strains] vary by regions,” says Lemieux. In the U.S., especially in the northeastern parts of the country, strains tend to be more invasive and disseminate through the body after infection, which could contribute to more severe disease. Versions of the bacteria more common in Europe tend to cause chronic skin conditions and neurological symptoms,

“We’re only scratching the surface of this,” says Lemieux of the knowledge represented by this genetic database, which he and his team uploaded to the public genetic research database GenBank, from the National Institutes of Health, for other scientists to study and analyze. “This paper is one brick in the foundation, and a valuable tool for the field.”