Why Does Lyme Disease Affect Specific Individuals

As the northeastern United States prepares for another Lyme disease season without an approved vaccine, more individuals are at increased risk of both acute Lyme disease (caused by B. burgdorferi infection) and postacute sequelae after Lyme disease.

Lyme disease has been a notifiable condition since 1991. Last year, approximately 89,000 cases were reported in the U.S., in states such as Pennsylvania.

To help understand the impact of this tick-transmitted disease, the journal Science Translational Medicine published two insightful studies.

Published on April 23, 2025, these studies investigate not only why Lyme disease continues to affect specific individuals but also which antibiotics are most effective in treating the disease.

One study offers insights into the presence of antigens from bacterial remnants transported to the liver, shedding light on the mechanisms behind the disease's persistence.

McClune et al. investigated how the B. burgdorferi peptidoglycan (PGBb) may contribute to the long-term consequences of Lyme disease. They observed that a particular form of PGBb could persist in the mouse liver for much longer than others, or even peptidoglycan from different bacteria, suggesting that PGBb could serve as a source of continuous antigen, thereby driving inflammation. 

The other study rigorously evaluates approved antibiotics, aiming to identify a safer and more effective alternative that can be administered at a lower dose than the standard treatment, doxycycline.

Piperacillin emerged as a compound that eradicated B. burgdorferi at low-nanomolar concentrations by specifically interfering with the unusual, multizonal peptidoglycan synthesis pattern common to the Borrelia clade.

Mechanistic in vitro studies identified the cellular target of piperacillin in B. burgdorferi, producing key insights that may explain both the specificity and efficacy of the compound.

Furthermore, in vivo studies using an experimental mouse infection model showed that piperacillin-treated animals received a 100-fold lower dose than the effective dose of doxycycline without affecting the murine microbiome.

These findings suggest that piperacillin may provide clinicians with an additional therapeutic option for Lyme disease.

These researchers wrote, 'By enhancing our understanding and opening the door to alternative treatment options, we may be able to improve outcomes for those battling this challenging illness.'

'Together, these findings could revolutionize our approach to Lyme disease, offering new hope for the millions affected in the United States each year,' the researchers concluded.

Shortly, an innovative Lyme disease vaccine candidate that is conducting late-stage clinical trials could become available in the U.S. But its pending approval will not be in time for use during the 2025 season.