# The natural release of unusual peptidoglycan fragments drives persistent Lyme disease symptoms in susceptible hosts

> **NIH NIH R01** · NORTHWESTERN UNIVERSITY · 2024 · $558,562

## Abstract

ABSTRACT
Lyme disease is the most reported vector-borne disease in the Northern Hemisphere. Lyme disease is caused
by the spirochetal bacterium¾Borrelia burgdorferi¾an unusual pathogen in that it is capable of causing severe
disease, despite lacking any recognizable virulence factors. Prompt therapy is often affective, but many patients
may still experience severe symptoms, chiefly Lyme arthritis. The reason(s) for persistent symptoms is poorly
understood and the most debated topic in the field. The lead investigator of this proposal discovered that B.
burgdorferi sheds ~45% of its peptidoglycan (PG)—the essential component of the bacterial cell-wall—from
inside the cell, into its environment. B. burgdorferi PG can be detected in the synovial fluid of Lyme arthritis
patients' months after oral and/or intravenous antibiotics. Experimental animal studies have shown that purified
B. burgdorferi PG alone, is capable of causing arthritis. We have shown that the chemical constituents of B.
burgdorferi PG are unlike any on the planet and real-time tracking studies indicate that these unique features
are associated with extended dwell times in discrete organs. Taken together, we hypothesize that the natural
release of unique B. burgdorferi PG fragments is responsible for driving Lyme arthritis, post-therapy, in
susceptible mammals, but we can target lingering fragments for therapeutic purposes. This proposal will critically
assess 1) what exactly is being released and what persists; 2) where and how the material persists; 3) the
relationship between Borreliae PG chemistry and persistent disease; 4) host factors that may contribute to PG-
induced arthritis; and 5) if targeted monoclonal antibody therapy is viable approach to treat patients suffering
from Lyme arthritis. Our studies will fill critical knowledge gaps in what is driving patient symptomology after
antibiotic therapy and may lead to new ways to treat patients when conventional options have failed.

## Key facts

- **NIH application ID:** 11144096
- **Project number:** 7R01AI178711-02
- **Recipient organization:** NORTHWESTERN UNIVERSITY
- **Principal Investigator:** Brandon Lyon Jutras
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $558,562
- **Award type:** 7
- **Project period:** 2023-06-15 → 2028-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/11144096

## Citation

> US National Institutes of Health, RePORTER application 11144096, The natural release of unusual peptidoglycan fragments drives persistent Lyme disease symptoms in susceptible hosts (7R01AI178711-02). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/11144096. Licensed CC0.

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