# SpoVG and PlzA Regulation of Lyme Disease Spirochete Infection Processes

> **NIH NIH R01** · UNIVERSITY OF KENTUCKY · 2021 · $724,619

## Abstract

v ABSTRACT
Bacterial infections require that the pathogen accurately produce essential factors at appropriate levels during
each stage of infection processes. Understanding how bacteria control levels of their proteins in response to
cues from their hosts provides important insights on microbial infectious properties. Such knowledge can also
reveal new targets for improved preventative and curative therapies.
The Lyme disease spirochete, Borrelia burgdorferi, survives in nature through cycles of infecting vertebrates
and ticks. The CDC calculates that there are approximately 300,000 new cases of human Lyme disease in the
USA each year. B. burgdorferi can persistently infect immunocompetent humans and other mammals for many
years. Failure to treat Lyme disease promptly and adequately can result in persistent debilitating effects or,
sometimes, death. Long-term infections may require extensive periods of antibiotic treatment. In order to better
treat Lyme disease, it is critical to develop a more thorough understanding of B. burgdorferi biology, including
the mechanisms by which the spirochete controls production of virulence factors.
We discovered that a borrelial protein, SpoVG, binds with specificity and high affinity to DNA and RNA.
Deletion of spoVG significantly impaired B. burgdorferi's ability to colonize ticks and be transmitted from ticks
to mammals. Dysregulation of spoVG transcription caused significant changes in bacterial physiology. We
further found that SpoVG directly interacts with another B. burgdorferi protein, PlzA, the Lyme spirochete's
cyclic-di-GMP-binding protein. Our studies revealed that PlzA is also a site-specific nucleic acid-binding
protein, and ΔplzA mutants are defective in their infectivity. Among the many regulated targets we identified for
SpoVG and PlzA is the antigenically-variable VlsE surface protein, which is essential for persistent B.
burgdorferi infection.
The planned studies will simultaneously investigate SpoVG and PlzA, as well as the effects of c-di-GMP on
their functions. These preliminary data stemmed from long-standing collaborations between the P.I. and co-
investigators of this proposal. Our combined efforts will yield a comprehensive view of the mechanisms through
which B. burgdorferi controls production of these critical regulatory factors, and deep insights on how SpoVG,
PlzA, and c-di-GMP regulate VlsE and other virulence-associated proteins.
In addition, many other pathogenic bacteria produce homologs of SpoVG, and our observations on B.
burgdorferi SpoVG bear similarities with the protein's known effects in other bacterial pathogens. To date, little
is known about how SpoVG affects virulence and physiology in any bacterial species. The interactions we
discovered between SpoVG and PlzA raise the possibilities that other bacteria also control SpoVG function
through c-di-GMP-binding proteins. Results of the planned investigations will provide useful insights on the
regulatory mechanisms and in...

## Key facts

- **NIH application ID:** 10135010
- **Project number:** 5R01AI144126-02
- **Recipient organization:** UNIVERSITY OF KENTUCKY
- **Principal Investigator:** Brian Stevenson
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $724,619
- **Award type:** 5
- **Project period:** 2020-04-01 → 2024-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10135010

## Citation

> US National Institutes of Health, RePORTER application 10135010, SpoVG and PlzA Regulation of Lyme Disease Spirochete Infection Processes (5R01AI144126-02). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10135010. Licensed CC0.

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