Jacob Lemieux, MD, DPhil and Pardis Sabeti, MD, DPhil



Research funded by Bay Area Lyme Foundation provides most comprehensive and geographically widespread whole genome sequencing of Lyme bacteria

Results may help inform future research and how physicians treat Lyme disease 

PORTOLA VALLEY, Calif., August 31, 2023—Bay Area Lyme Foundation, a leading sponsor of Lyme disease research in the US, today announced the results of the most comprehensive whole genome sequencing study of Borrelia burgdorferi, the bacteria that causes Lyme disease—a condition affecting nearly 500,000 new patients annually. Published in the peer-reviewed journal PLOS Pathogens, the study is the first to define the connection between genomic markers and symptom severity, confirming that RST1 OspC type A strains, which are the most common type of Borrelia bacterial strains found in the Northeast, are associated with more disseminated infection and thus more severe Lyme disease. These new discoveries will help inform physicians that different strains of the Lyme disease bacteria in the US may cause more severe Lyme disease symptoms, which may include joint swelling, debilitating fatigue, memory loss, headaches and serious inflammation of the heart and brain.

“Dissemination from the site of inoculation to organs such as the heart, brain and joints is a key step in the development of severe Lyme disease. Up until now, the bacterial genes and plasmids associated with dissemination in humans had not yet been identified,” said first author Jacob Lemieux, MD, DPhil, Bay Area Lyme Foundation Emerging Leader Award winner, an infectious disease staff physician at Massachusetts General Hospital and Assistant Professor at Harvard Medical School and an Associate Member of the Broad Institute of MIT and Harvard. “This work provides important clues into the bacterial genetic basis of dissemination and therefore suggests candidates for further study, including proteins to target for therapeutics and vaccines aimed at preventing dissemination.”

The new study also identifies the genetic changes that distinguish more virulent strains, including an enlarged genome size, a unique set of plasmids, and an expanded set of surface-exposed lipid-modified proteins called lipoproteins.

Pardis Sabeti, MD, DPhil, professor at Harvard University, Institute member of the Broad Institute of MIT and Harvard, a Howard Hughes Medical Investigator and co-lead author added, “This research will lay the foundation for developing sensitive diagnostics for Lyme disease and help physicians refine treatment plans, arming them with a better understanding of Lyme disease bacterial strains and their clinical manifestations.”

The researchers published the whole genome sequence and analysis of 299 patient-derived B. burgdorferi samples (isolates) from the Northeastern (Massachusetts, New York, Rhode Island and Connecticut) and Midwestern US and Central Europe. The B. burgdoferi genome is made up of one long linear strip of DNA and 20-25 circular DNA plasmids. The researchers systematically determined the whole genome sequences using ribosomal spacer type (RST), outer surface protein C (OspC), and multilocus sequence typing (MLST), finding that clusters of genes are inherited in blocks through strain-specific patterns of plasmids and are associated with invasive infection and more severe disease manifestations.

The research highlights how evolution, geography, and differences in strain genetic diversity contribute to clinical manifestations and infections throughout the United States and Central Europe, laying the foundation for further research into, and treatment of Lyme disease.  For example, Lyme arthritis is more often reported in the US compared to Europe, likely because the infection in the US is derived mostly from the B. burgdorferi strains which are more arthritogenic. The study also showed that strains with OspC, (a protein on the surface of the bacteria) type A appear to be common among patients in the Northeastern US. This study further supports previous research that strains with OspC type A are the most virulent of the strains of B. burgdorferi sensu stricto found in the US. In a previous study, approximately 90% of Northern Californian patients were infected with B. burgdorferi OspC type A, and these patients presented with more severe disease.

“This monumental study shows the importance of developing diagnostics capable of detecting the specific B. burgdorferi strain (or strains) with which a patient has been infected. One-size-fits-all antibiotic treatment for Lyme may not be the most appropriate strategy for treating patients and preventing persistent symptoms. This new information may help physicians more easily determine a more tailored treatment regimen at the outset of infection,” said Wendy Adams, research grant director, Bay Area Lyme Foundation. “Supporting this important genomic study of the Lyme bacteria will lead to more thorough understanding of Lyme disease, and hopefully improved diagnostics and therapeutics for patients.”

Study co-authors Dr. Sabeti and John Branda, MD, who is also an Emerging Leader Award winner, both of Harvard and the Broad Institute have also received funding from the Bay Area Lyme Foundation.

Whole genome analysis of B. burgdoferi has been limited to date due to technical challenges of

sequencing and assembly and difficulties of obtaining samples from cases of human disease. The samples were collected over three decades across Northeastern and Midwestern US and Central Europe from 1992-2021, primarily from patients who presented with erythema migrans, an initial skin rash of the Lyme disease infection.

This research is a culmination of collaboration between researchers at Massachusetts General Hospital, Harvard Medical School, Broad Institute of MIT and Harvard, New York Medical College, East Carolina University, University of Ljubljana, NY State Wadsworth Center, University Medical Center Ljubljana, University of Wisconsin, Tufts University, Department of Molecular Biology and Microbiology Harvard University, Harvard T.H. Chan School of Public Health.

About Lyme disease
The most common vector-borne infectious disease in the US, Lyme disease is a potentially disabling infection caused by bacteria transmitted through the bite of an infected tick to people and pets, and potentially passed from a pregnant mother to her unborn baby. If caught early, most cases of Lyme disease can be effectively treated, but it is commonly misdiagnosed due to lack of awareness and inaccurate diagnostic tests. There are approximately 500,000 new cases of Lyme disease each year, according to statistics released in 2018 by the CDC. As a result of the difficulty in diagnosing and treating Lyme disease, up to two million Americans may be suffering from the impact of its debilitating long-term symptoms and complications, according to Bay Area Lyme Foundation estimates.

About Bay Area Lyme Foundation
Bay Area Lyme Foundation, a national organization committed to making Lyme disease easy to diagnose and simple to cure, is the leading public not-for-profit sponsor of innovative Lyme disease research in the US. A 501c3 organization based in Silicon Valley, Bay Area Lyme Foundation collaborates with world-class scientists and institutions to accelerate medical breakthroughs for Lyme disease. It is also dedicated to providing reliable, fact-based information so that prevention and the importance of early treatment are common knowledge. A pivotal donation from The LaureL STEM FUND covers overhead costs and allows for 100% of all donor contributions to the Bay Area Lyme Foundation to go directly to research and prevention programs. For more information about Lyme disease or to get involved, visit www.bayarealyme.org or call us at 650-530-2439.

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Media contact:
Tara DiMilia
Phone: 908-369-7168


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