# Regulatory Network of the Lyme Disease Pathogen

> **NIH NIH R01** · INDIANA UNIVERSITY INDIANAPOLIS · 2024 · $470,225

## Abstract

ABSTRACT
Lyme disease is an emerging tick-borne disease and an important public health problem in the
United States. The causative agent, Borrelia burgdorferi (Bb), must dramatically alter its gene
expression as it traverses its enzootic cycle between the arthropod vector (Ixodes ticks) and rodent
mammalian hosts. In the past several years, the PI’s previous work discovered a central regulatory
pathway, the RpoS pathway, in B. burgdorferi. The RpoS pathway is a gatekeeper for B. burgdorferi
to exit from ticks and infect mammals. RpoS control many antigens and virulence factors for
mammalian infection. The PI’s previous work, along with others, demonstrated that transcriptional
activation of rpoS is under the control of the sigma factor 54 (σ54) and a bacterial enhancer-binding
protein (EBP), Rrp2. It is well established in other bacteria that EBP is essential and sufficient to
activate a σ54-type promoter both in vivo and in vitro. Surprisingly, another regulator, BosR, was
discovered independently by two groups a decade ago and showed that BosR directly regulates rpoS
transcription from its σ54-type promoter. How BosR fits into this pathway is a significant gap in our
understanding of the RpoS pathway. Based on our Preliminary Studies, we propose a provocative
hypothesis: BosR is not a transcriptional activator; instead, BosR is a novel RNA binding protein that
binds to rpoS mRNA and stabilizes its turnover. We will test this hypothesis in Aim 1. Given that few
factors have been identified for regulating the RpoS pathway, we have successfully developed a
genetic screen for identifying genes that influence the regulation of RpoS. Such screen allows us to
identify genome-wide novel factors that modulate the RpoS pathway, uncover a comprehensive
picture of how the RpoS pathway is regulated and how multi-signals influence the pathway in the
enzootic cycle of Bb between the tick vector and the mammalian host, which is proposed in Aim 2.

## Key facts

- **NIH application ID:** 10857343
- **Project number:** 5R01AI083640-12
- **Recipient organization:** INDIANA UNIVERSITY INDIANAPOLIS
- **Principal Investigator:** X. Frank Yang
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $470,225
- **Award type:** 5
- **Project period:** 2009-07-01 → 2028-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10857343

## Citation

> US National Institutes of Health, RePORTER application 10857343, Regulatory Network of the Lyme Disease Pathogen (5R01AI083640-12). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10857343. Licensed CC0.

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