Exploiting the Natural Release of Unique Peptidoglycan Fragments to Directly Diagnose Lyme Disease
Abstract
Lyme disease is one of the most reported bacterial infections in the United States and yet we are likely only capturing approximately 6% of the cases. Patients and physicians are frustrated with the current state of Lyme disease diagnostics. In no other bacterial infection of this magnitude do we rely on an indirect test. Indirect tests are (1) insensitive, (2) inaccurate, (3) take weeks to months, and (4) in the case of serological antibody testing, only report on exposure. Many aspects of Lyme disease are surrounded by controversy and misinformation, but one is not – rapid treatment leads to better outcomes for Service Members, patients, and anyone affected by Lyme disease. We need radical and rapid changes to ensure no one suffers with this disease. We can do better. Improved methods that accurately diagnose an acute Lyme disease infection have been hampered by a lack of both targets and vision by the research community. While we were studying fundamental aspects of Borrelia burgdorferi – the causative agent of Lyme disease – we made a serendipitous discovery. As the bacterium replicates, it sheds its peptidoglycan cell-wall. Peptidoglycan is an internal layer of the bacterium that makes up approximately 10% of the entire cell. Almost all bacteria have peptidoglycan, but the molecular features of B. burgdorferi peptidoglycan are unlike any other on the planet. The components, while unique, are shared by all the Lyme disease causing Borrelia. Since B. burgdorferi peptidoglycan is (1) released, (2) abundant, and (3) unique we believe that this is the perfect biomarker for diagnostic purposes. Biomarkers are unique signatures that can be accurately and reproducibly measured and indicate the presence of a component in a system. In this case, the presence of B. burgdorferi peptidoglycan in a human system acts as an unbiased biomarker indicative of an active Lyme disease infection. We have created several monoclonal antibodies that are able to detect different pieces the bacterium is releasing as it grows. Using these monoclonal antibodies, we will develop multiple, simple, rapid tests that are no more complicated than a COVID-19 PCR test. The best performing test(s) will be put through a series of exhaustive, blinded trials to critically determine (1) when they work, (2) when they fail, and (3) how we can improve. We have re-envisioned Lyme disease diagnostics. Our strategy is sound and the results from preliminary tests are very promising. We may be on the cuspid of a revolutionary leap in Lyme disease diagnostics – one which can diagnose a patient within hours of infection.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Jan 04, 2024
- Source ID
- HT94252311042
Entities
People
- Brandon Jutras
Organizations
- United States Army
- Virginia Tech