# Regulatory Pathways in Borrelial Pathogenesis

> **NIH NIH R01** · TEXAS A&M UNIVERSITY HEALTH SCIENCE CTR · 2024 · $663,145

## Abstract

PROJECT SUMMARY
 The etiologic agent of Lyme Disease, Borrelia burgdorferi (Bb), is the leading arthropod-borne infection in the
United States with over 470,000 cases diagnosed annually. Given that Lyme Disease is a significant public
health concern, studies addressing how Bb establishes and maintains infection are vital to evaluating its
pathogenic potential and developing prevention or therapeutic strategies. It is well known that Bb modifies its
transcriptional profile throughout its pathogenic lifecycle, particularly during transmission from the arthropod
vector into mammals. BosR is an important transcriptional regulator that functions as a global metalloregulatory
protein and alters the expression of genes needed for mammalian colonization. Specifically, BosR is required
for experimental infection in mice and is needed for the activation of the RpoS/RpoN/Rrp2 cascade that drives
the expression of genetically unlinked genes, including virulence determinants required for Bb infection. While
there is no doubt that the BosR-dependent regulation of rpoS is important to borrelial infectivity, there are
additional genes that BosR regulates either directly or indirectly that may factor into Bb infection. How BosR is
linked to this complex regulatory network has not been thoroughly addressed. Here, several novel BosR
regulatory functions are described, heretofore unknown, including the recognition of RNA by BosR. The
Preliminary Data shows that BosR binds to small non-coding RNA and exhibits chaperone activity suggesting
that BosR forms a complex with sRNAs that binds to Bb transcripts and targets them for degradation or enhanced
translation. This form of post-transcriptional regulation by BosR represents a new and innovative regulatory
scheme that adds to its known DNA binding activity. In Aim 1, a subset of sRNAs that BosR binds will be
evaluated, the transcripts recognized by the BosR::sRNA complex identified, and a link with the BosR-associated
sRNAs to borrelial pathogenesis established. In Aim 2, recent ChIP-seq data will be mined to assess novel BosR
DNA binding. Preliminary binding studies confirmed the ChIP-seq data for two targets and suggested that the
redox status and metal coordination of BosR may alter DNA binding. BosR DNA binding will be analyzed to
determine how the redox and metal binding status of BosR changes the target sequences recognized. Unique
BosR binding motifs will be tracked, and a consensus sequence ascertained. Finally, experiments will be
conducted to determine the phenotype of a bosR mutant that ectopically produces RpoS to query the direct role
of BosR in Bb infection. Taken together, this proposal will provide new appreciation into how BosR-mediated
transcriptional and post-transcriptional regulation ensues and novel insight into how BosR integrates the redox
status of Bb to affect nucleic acid binding and borrelial pathogenesis.

## Key facts

- **NIH application ID:** 10884367
- **Project number:** 5R01AI170940-03
- **Recipient organization:** TEXAS A&M UNIVERSITY HEALTH SCIENCE CTR
- **Principal Investigator:** Jenny A. Hyde
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $663,145
- **Award type:** 5
- **Project period:** 2022-08-05 → 2026-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10884367

## Citation

> US National Institutes of Health, RePORTER application 10884367, Regulatory Pathways in Borrelial Pathogenesis (5R01AI170940-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10884367. Licensed CC0.

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