# Borrelia gene products critical for natural infection cycle

> **NIH NIH R01** · UNIV OF MARYLAND, COLLEGE PARK · 2024 · $474,580

## Abstract

PROJECT SUMMARY/ABSTRACT
Lyme borreliosis, also known as Lyme disease, remains a prevalent tick-borne infection in many parts of the
world. In the United States alone, there are over 300,000 new cases occurring each year. The infection is
caused by Borrelia burgdorferi sensu lato, which is a group of atypical extracellular bacterial pathogens that
survive in nature through a complex enzootic infection cycle, involving ticks belonging to the Ixodes scapularis
complex and an array of vertebrate hosts, most commonly wild rodents. Despite serious efforts to control the
infection over the past several decades, the infection persists, largely due to the absence of effective control
measures against tick infestation, lack of human vaccines, difficulties in diagnosis of early infection, and clinical
complications associated with treatment using currently-available antimicrobials. Specifically, several months
after standard-care antibiotic therapy, a subset of patients can experience a series of persistent or relapsing
symptoms, known as chronic Lyme disease or post-treatment Lyme disease syndrome, for which further
treatment options remain unavailable. Therefore, the development of vaccines and new drugs is highly
warranted to combat Lyme disease. This project pursues a long-term goal to understand the biological
significance of a critical set of microbial virulence determinants and gain knowledge necessary for the
development of new therapeutic strategies to intervene with Lyme borreliosis. The emphasis is on protein-
protein interactions essential for pathogen infection and persistence in the host, and the goal is to provide
comprehensive structural and functional information that defines the biological significance of three spirochete
proteins annotated as BB0323, BB0238, and BB0104 (BbHtrA), each of which either independently or as a
complex are essential for infection. The previous project cycle demonstrated that the targeted deletion or
alteration of either protein partners or short binding epitopes impact protein stability and render the pathogen
non-infectious in a mammalian host. The overall objective of the current proposal is to further focus on
BB0323 and associated proteins in order to: 1) define the specific events of protein maturation, 2)
determine protein-protein interactions, and 3) contribute to the determination of their structures to
better understand their roles in dictating spirochete infection in mammals and transmission from ticks.
These studies will enlighten our fundamental knowledge of the atypical biology of spirochetes and will facilitate
the design of non-traditional anti-infective strategies to combat Lyme borreliosis, including the development of
vaccines, small molecule drugs, and biologics.

## Key facts

- **NIH application ID:** 10895515
- **Project number:** 5R01AI080615-12
- **Recipient organization:** UNIV OF MARYLAND, COLLEGE PARK
- **Principal Investigator:** UTPAL PAL
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $474,580
- **Award type:** 5
- **Project period:** 2009-07-01 → 2026-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10895515

## Citation

> US National Institutes of Health, RePORTER application 10895515, Borrelia gene products critical for natural infection cycle (5R01AI080615-12). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10895515. Licensed CC0.

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