# Analysis of the DksA regulon in the Lyme disease spirochete

> **NIH NIH R21** · UNIVERSITY OF SOUTH FLORIDA · 2021 · $224,250

## Abstract

ABSTRACT
Stringent response is a physiological mechanism utilized by bacteria to adapt to nutrient deprivation and many
other stresses. In Borrelia burgdorferi (Bb), the etiological agent of Lyme disease, stringent response is mediated
by both the alarmone nucleotides (p)ppGpp and the RNA polymerase-binding protein DksA. Recently, we found
that DksA plays an essential role in regulating Bb's virulence. First, dksA is highly expressed in infected animals
and is required by Bb to infect the mammalian hosts. Second, DksA is critical for Bb's optimal growth. Third,
DksA is required by Bb to cope with metabolic stress. Finally, in addition to function as a stringent response
regulator, DksA promotes the transcription and/or translation of genes contributing to Bb's survival in the host.
These combined data give rise to our hypothesis that DksA is a master regulator governing Bb's virulence gene
expression. This hypothesis will be addressed in two Specific Aims. In Aim 1 of this proposal, we will determine
the contribution of DksA to Bb's survival and persistence in ticks. In Aim 2, we will identify genes regulated by
DksA under various in vitro and in vivo conditions. These combined studies will (i) define the entire DksA regulon;
and (ii) provide a transformative understanding of the in vivo importance of DksA and the regulon. Resultant
findings could lead to the development of new strategies to prevent and/or treat Lyme disease.

## Key facts

- **NIH application ID:** 10189812
- **Project number:** 1R21AI159061-01
- **Recipient organization:** UNIVERSITY OF SOUTH FLORIDA
- **Principal Investigator:** Zhiming Ouyang
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $224,250
- **Award type:** 1
- **Project period:** 2021-03-19 → 2023-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10189812

## Citation

> US National Institutes of Health, RePORTER application 10189812, Analysis of the DksA regulon in the Lyme disease spirochete (1R21AI159061-01). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10189812. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*