Author ORCID Identifier

https://orcid.org/0009-0004-9255-1367

Semester

Spring

Date of Graduation

2026

Document Type

Dissertation

Degree Type

PhD

College

Eberly College of Arts and Sciences

Department

Biology

Committee Chair

Timothy Driscoll

Committee Member

Mariette Barbier

Committee Member

Rita Rio

Committee Member

Jennifer Hawkins

Committee Member

Jennifer Gallagher

Abstract

Lyme disease is the most common vector-borne disease in the United States with an estimated yearly incidence rate of more than 300,000 cases. Borreliella burgdorferi, the etiological agent of Lyme disease, is transmitted by the bite of an infected Ixodes scapularis tick and can cause debilitating pathologies affecting numerous body systems. Symptoms include fever, fatigue, joint pain, and a characteristic bull’s eye rash (erythema migrans) at the site of the tick bite. The timely and appropriate use of antibiotics effectively treats early Lyme disease; however, uncomfortable side effects reduce treatment compliance. If left untreated, long-term complications can arise including facial palsy, heart complications, central nervous system inflammation, and chronic joint pain. There is currently no human-approved vaccine for Lyme disease. With the growing incidence of cases each year, an efficacious vaccine is increasingly needed.

Peptidoglycan (PG) is a prominent cell wall component and crucial for bacterial cell growth and division. B. burgdorferi contains a complete PG synthesis pathway except for the initial steps that generate N-acetylglucosamine (NAG). It is hypothesized that B. burgdorferi acquires NAG from the extracellular media by means of one or more importers. In this dissertation, I explored the research question: Is the peptidoglycan import pathway a source of potential vaccine targets for Lyme disease? To address this question, I developed 3 specific aims.

In Aim 1, I validated a laboratory model for establishing persistent infection of B. burgdorferi within its primary vector, I. scapularis. This model was used to confirm the infectious nature of a GFP-expressing strain of B. burgdorferi. I also used comparative genomics to characterize this GFP-expressing strain and facilitate its use as a tool in future B. burgdorferi research.

In Aim 2, I characterized the expression of several genes thought to be involved in NAG acquisition. The premise of this Aim was that cold-blooded ticks present an abundance of chitobiose, while warm-blooded mammals present an abundance of NAG, leading B. burgdorferi to switch between import systems. I hypothesized that either substrate availability or temperature would influence expression of these genes. Results of this Aim instead support a model whereby this pathogen can assemble an import system from a variety of subunits with relaxed specificity.

In Aim 3, I used bioinformatics to explore the taxonomic representation and evolutionary lineage of the NAG acquisition genes investigated in Aim 2. I hypothesized that chbABC would present similar lineages as a putative functional operon. Results of this Aim instead demonstrate that chbC exhibits a distinct lineage from chbA and chbB, and only one of the NAG acquisition genes showed a strong signal of vertical inheritance.

Collectively, this work demonstrates that the GFP expressing strain of B. burgdorferi is infectious and can be a valuable tool in future Lyme disease research and reveals unanticipated complexity in the acquisition of nutrients required for PG synthesis. This work provides a foundation for future studies aimed at developing targeted therapeutics and transmission-blocking strategies against Lyme disease.

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