# Defining global gene regulation and virulence determinants of relapsing fever spirochetes

> **NIH NIH P20** · UNIV OF ARKANSAS FOR MED SCIS · 2020 · $247,415

## Abstract

PROJECT SUMMARY/ABSTRACT
 The vector-borne spirochetes that cause relapsing fever are transmitted to humans by either soft ticks or
human body lice. Despite identification of the etiological agents of relapsing fever over 100 years ago, very
little information exists regarding their pathogenesis. Although relapsing fever is more common in developing
countries, tick-borne relapsing fever (TBRF) occurs in areas of the U.S. where Ornithodoros species of soft ticks,
the vectors for TBRF spirochetes, are endemic. During their natural enzootic cycle, vector-borne spirochetes
exist in two distinct niches found within the arthropod vector and the vertebrate. It is well established that Lyme
disease spirochetes must undergo significant changes in global gene expression to allow them to adapt to
these two diverse environments, and a great deal of information exists regarding the regulatory networks that
control this bacterial adaptive response. However, the correlate that occurs in TBRF spirochetes to facilitate
vector-mediated transmission and mammalian infection remains undefined. Our overall goal is to expand our
knowledge of the pathogenesis of TBRF spirochetes and to identify virulence determinants (e.g., virulence
factors and regulatory components) required during mammalian infection. We hypothesize that TBRF
spirochetes must sense environmental temperature and utilize this stimulus to control expression of genes
essential for mammalian infection and vector transmission. In preliminary experiments, we first defined the
global temperature-dependent gene response that occurs in Borrelia turicatae, one of the major Borrelia
species responsible for TBRF in the U.S., and then used these data to establish a set of genes that will be
characterized during the course of studies in this project. Aim 1 seeks to identify cis- and trans-regulatory
elements responsible for controlling the expression of temperature-responsive genes in B. turicatae. In Aim 2,
we will use targeted mutagenesis to inactivate individual temperature-responsive genes in B. turicatae and
identify bacterial factors required for infection and pathogenesis. These aims will provide critical knowledge
regarding differential gene regulation occurring in TBRF spirochetes during transmission and infection, and
identify virulence determinants required by the bacteria to cause disease. This research is aligned with the
COBRE program's focus on microbial pathogenesis by defining molecular determinants of TBRF spirochetes
that contribute to adaptation and interaction within the mammalian host. Regulators and virulence factors
identified in this project represent potential targets against which future therapeutic interventions and/or
diagnostics for TBRF could be developed. The further characterization of these virulence determinants will be
the focus of future R01 grant proposals.

## Key facts

- **NIH application ID:** 9925789
- **Project number:** 5P20GM103625-09
- **Recipient organization:** UNIV OF ARKANSAS FOR MED SCIS
- **Principal Investigator:** Jon Scott Blevins
- **Activity code:** P20 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $247,415
- **Award type:** 5
- **Project period:** — → —

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9925789

## Citation

> US National Institutes of Health, RePORTER application 9925789, Defining global gene regulation and virulence determinants of relapsing fever spirochetes (5P20GM103625-09). Retrieved via AI Analytics 2026-06-12 from https://api.ai-analytics.org/grant/nih/9925789. Licensed CC0.

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