# Virulence regulation by BadR in the Lyme disease spirochete

> **NIH NIH R01** · UNIVERSITY OF SOUTH FLORIDA · 2022 · $373,750

## Abstract

ABSTRACT
Borrelia burgdorferi (Bb), the etiological agent of Lyme disease, maintains itself in nature via a complex life cycle
involving an arthropod (tick) vector and small mammals. During its cycle between ticks and mammals, Bb
undergoes dramatic adaptive changes in order to interact with and adapt to these two disparate niches.
Previously, we found that BadR, a homologue of ROK repressors, binds to the rpoS promoter region and
represses the expression of rpoS. Moreover, our preliminary findings have suggested that BadR has much
broader biological relevance to the life cycle of Bb other than repressing rpoS expression. First, BadR is required
for Bb's optimal growth. Second, BadR plays a vital role in the establishment of mammalian infection. Contrary
to the wild-type strain, a badR deletion mutant is incapable of infecting mice, suggesting that BadR governs
expression of key effector proteins associated with Bb's survival in the host. Phenotypic defects of the badR
mutant in mice infection are NOT related to the well documented RpoN-RpoS regulatory pathway, because all
of BosR, Rrp2, RpoN, and RpoS are still produced in the badR mutant. In fact, our preliminary global
transcriptomic analyses using RNA-seq have identified numerous BosR/RpoS-independent genes regulated by
BadR. In addition, we found that badR is expressed throughout Bb's tick-mammal infectious cycle. These
combined data give rise to our hypothesis that BadR is a master regulator governing Bb's host adaption and
virulence expression. This hypothesis will be addressed in two Specific Aims. In Aim 1 of this proposal, we will
employ global transcriptome/proteome profiling to define the entire BadR regulon under various in vitro and in
vivo conditions. In Aim 2, we will select BadR-regulated genes based on our global transcriptome/proteome
analyses and characterize their contributions to Bb's infectious cycle. These combined studies will (i) refine our
knowledge on BadR-mediated gene regulation; (ii) provide a transformative understanding of the in vivo
importance of the regulon; and (iii) identify novel virulence determinants. Resultant findings could lead to the
development of new strategies to prevent and/or treat Lyme disease.

## Key facts

- **NIH application ID:** 10376875
- **Project number:** 5R01AI152983-02
- **Recipient organization:** UNIVERSITY OF SOUTH FLORIDA
- **Principal Investigator:** Zhiming Ouyang
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $373,750
- **Award type:** 5
- **Project period:** 2021-03-24 → 2026-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10376875

## Citation

> US National Institutes of Health, RePORTER application 10376875, Virulence regulation by BadR in the Lyme disease spirochete (5R01AI152983-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10376875. Licensed CC0.

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