For decades, Lyme disease has posed significant challenges to both physicians and patients. This debilitating illness, caused by the corkscrew-shaped bacterium Borrelia burgdorferi, can linger for months if untreated, leading to symptoms such as fever, fatigue, and painful inflammation. In a groundbreaking study, scientists from Northwestern University and the Uniformed Services University (USU) have identified a surprising vulnerability in this resilient bacterium, potentially paving the way for innovative therapeutic strategies.
The study, set to be published in the journal mBio on November 13, reveals that manganese, a metal that helps B. burgdorferi shield itself from the host’s immune system, is also a critical weakness. Researchers found that manipulating manganese levels could render the bacteria vulnerable to immune responses or treatments they would typically resist.
The Double-Edged Role of Manganese
According to the study, manganese plays a dual role in the survival of B. burgdorferi. While it acts as a protective armor, it also represents a potential Achilles’ heel. “Our work shows that manganese is a double-edged sword in Lyme disease,” said Brian Hoffman, a co-leader of the study and the Charles E. and Emma H. Morrison Professor of Chemistry and Molecular Biosciences at Northwestern University. “It’s both Borrelia’s armor and its weakness. If we can target the way it manages manganese, we could open doors for entirely new approaches for treating Lyme disease.”
Hoffman, alongside Michael Daly, an emeritus professor of pathology at USU, spearheaded this research. Their findings suggest that disrupting the bacterium’s manganese management could leave it defenseless against the host’s immune system.
Lyme Disease: A Growing Concern
Since the 1980s, Lyme disease has seen a dramatic increase in prevalence across North America and globally. The Centers for Disease Control and Prevention estimates that approximately 476,000 people in the United States are diagnosed with Lyme disease each year. Despite its widespread impact, no approved vaccines exist, and long-term antibiotic use remains problematic.
“Although antibiotics harm B. burgdorferi, they also kill beneficial gut bacteria,” Daly explained. “Lyme disease is transmitted through tick bites and — if not treated promptly — can cause lingering effects by attacking the patient’s immune, circulatory, and central nervous systems.”
Innovative Research Techniques
The research team employed advanced technologies to explore the role of manganese in B. burgdorferi‘s defenses. Using electron paramagnetic resonance (EPR) imaging and electron nuclear double resonance (ENDOR) spectroscopy, the scientists created a molecular map detailing the forms and locations of manganese within the bacteria. This map unveiled a two-tier defense system involving an enzyme called MnSOD and a pool of manganese metabolites.
“Our study demonstrates the power of EPR and ENDOR spectroscopies for uncovering hidden biochemical mechanisms in pathogens,” Hoffman said. “Without these tools, B. burgdorferi‘s defense system and weak spots would have remained invisible.”
The researchers discovered that the bacteria constantly juggle manganese distribution between MnSOD enzymes and the metabolite pool. An imbalance — either too little or too much manganese — compromises the bacterium’s defenses, leaving it susceptible to damage and stress.
Future Implications for Lyme Disease Treatment
This discovery opens the door to potential new therapies for Lyme disease. Future treatments could aim to starve the bacterium of manganese, disrupt its protective complexes, or induce toxic overload. Any of these approaches could enhance the host’s ability to combat the infection.
“By disrupting the delicate balance of manganese in B. burgdorferi, it may be possible to weaken the pathogen during infection,” Daly said. “Manganese is an Achilles’ heel of its defenses.”
The study, “EPR spectroscopy reveals antioxidant manganese defenses in the Lyme disease pathogen Borrelia burgdorferi,” was supported by the Congressionally Directed Medical Research Programs’ Tick-borne Disease Research Program and the National Institutes of Health, among other funders. These findings mark a significant step forward in understanding and potentially controlling Lyme disease, offering hope for more effective treatments in the future.
