After years of research an international team of scientists has unraveled the genetic makeup of 47 strains of known and potential Lyme disease-causing bacteria. The work paves the way toward more accurate diagnostic tests and targeted treatment against the many strains of Borrelia burgdorferi, the cause of Lyme disease, which remains the most prevalent tick-borne disease in the United States and Europe. The team’s findings are published in the journal mBio.

Lyme disease affects hundreds of thousands of people each year. In the United States alone case numbers are approaching 500,000 per year. If left untreated, the infection can spread to joints, the heart and nervous system and cause more severe complications. The authors say that with climate change and potentially other environmental factors, cases of Lyme disease may only keep increasing worldwide. Additionally, some of the Borrelia species that they genetically sequenced in this study that do not cause disease now could be a genetic reservoir for the future evolution of these species.

“This is a seminal study with not only new genetic findings that map out the genomes of 47 strains of Borrelia, it is a body of work that provides researchers with data and tools going forward to better tailor treatment against all causes of Lyme disease and provides a framework toward similar approaches against other infectious diseases caused by pathogens,” says Benjamin Luft, MD, the Edmund D. Pellegrino Professor of Medicine at the Renaissance School of Medicine at Stony Brook University, and an internationally recognized expert in the investigation and treatment of Lyme disease. Stony Brook Medicine has a clinic dedicated to treating Lyme disease and all tick-borne infections and is home to the Regional Tick-Borne Disease Resource Center.

The research team encompassed investigators from more than a dozen research institutions around the world. In combination, they sequenced the complete genomes of Lyme disease bacteria representing all 23-known species in the group. Most of these hadn’t been sequenced before this effort. The sequencing included multiple strains of the bacteria most commonly associated with human infections and species not previously known to cause disease in humans.

By comparing these genomes, the researchers reconstructed the evolutionary history of Lyme disease bacteria, tracing the origins back millions of years. They discovered the bacteria likely originated before the breakup of the ancient supercontinent Pangea, which helps explain the current worldwide distribution.

The study also revealed how these bacteria exchange genetic material within and between species. This process, known as recombination, allows the bacteria to rapidly evolve and adapt to new environments. The researchers identified specific hot spots in the bacterial genomes where this genetic exchange occurs most frequently, often involving genes that help the bacteria interact with their tick vectors and animal hosts.

“By understanding how these bacteria evolve and exchange genetic material, we’re better equipped to predict and respond to changes in their behavior, including potential shifts in their ability to cause disease in humans,” explains Weigang Qiu, PhD, Senior Author and Professor of Biology at City University of New York.

To facilitate ongoing research, the team has developed web-based software tools (BorreliaBase.org) that enables scientists to compare Borrelia genomes and identify determinants of human pathogenicity.

Future collaborative research by the international team includes a plan to expand the genome analysis to include more strains of Lyme disease bacteria, particularly from understudied regions. They will also investigate the specific functions of genes unique to disease-causing strains, which could reveal new targets for therapeutic interventions.

The research leading to this published work was funded primarily by the National Institute of Health’s National Institutes of Allergy and Infectious Diseases (NIAID). The research was also supported by the Steve and Alexandra Cohen Foundation.

Twenty authors, including Dr. Luft,  are listed on the paper. Leading collaborators and co-authors include Sherwood Casjens of the University of Utah School of Medicine, Weigang Qiu of the City University of New York, Steven Schutzer of Rutgers New Jersey Medical School, Claire Fraser and Emmanuel Mongodin of the University of Maryland School of Medicine, and Richard G. Morgan of New England BioLabs.