# Defining the host and pathogen determinants of peptidoglycan induced pathophysiology in Lyme disease

> **NIH NIH R01** · NORTHWESTERN UNIVERSITY · 2024 · $541,558

## Abstract

ABSTRACT
Accounting for ten times more cases than all of vector-borne diseases combined in the United States, Lyme
disease is an escalating and pervasive problem. Upon infection with the Lyme disease agent—Borrelia
burgdorferi— patients experience mild, flu-like symptoms that can go on to become more severe. In later stages,
even after antibiotic therapy, patients can experience heart, joint, and neurological problems. 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. When injected into a mouse, B.
burgdorferi PG alone, is capable of causing arthritis. Virtually all bacteria have PG but, as it turns out, B.
burgdorferi PG is chemically unique and unlike any previously studied. Real-timing PG tracking experiments in
live animals suggest that the unique features of B. burgdorferi muropeptides contributes to both half-life and
discrete tissue localization. These findings led us to hypothesize that shed B. burgdorferi PG fragments contain
unique chemical signature(s) that are required for persistence, Lyme disease pathogenesis, and arthritis. This
proposal will critically test these theories and provide a comprehensive understanding of 1) how and 2) where
PG is able to persist; 3) what molecular features contribute to PG persistence; 4) the mechanistic details that
underlie PG-induced Lyme arthritis; and 5) the importance of muropeptide shedding in the natural life cycle of B.
burgdorferi. Our proposed studies challenge conventional thinking and may lead to a paradigm shift in how we
understand Lyme disease pathogenesis. They may also lead to novel ways to treat patients suffering with Lyme
disease and post-treatment Lyme disease syndrome, even after conventional therapies have failed.

## Key facts

- **NIH application ID:** 11139176
- **Project number:** 7R01AI173256-02
- **Recipient organization:** NORTHWESTERN UNIVERSITY
- **Principal Investigator:** Brandon Lyon Jutras
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $541,558
- **Award type:** 7
- **Project period:** 2024-08-01 → 2027-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/11139176

## Citation

> US National Institutes of Health, RePORTER application 11139176, Defining the host and pathogen determinants of peptidoglycan induced pathophysiology in Lyme disease (7R01AI173256-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/11139176. Licensed CC0.

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