# Understanding Unique Aspects of Motility and Chemotaxis in Borrelia burgdorferi

> **NIH NIH R01** · VIRGINIA COMMONWEALTH UNIVERSITY · 2024 · $473,229

## Abstract

SUMMARY
Lyme disease bacterium Borrelia burgdorferi (Bb) is highly motile and can traverse complex environments inside
mammalian and arthropod hosts during its infectious cycle. The central hypothesis of this application is that the
motility and chemotaxis of Bb constitute a distinct paradigm and play a pivotal role in the host-vector cycle as well
as in the disease process, including invasion, dissemination, tissue tropism, and immune evasion. During the last
two funding cycles, we revealed several unique aspects of Bb motility and chemotaxis; however, their underlying
molecular mechanisms and precise roles in the disease process remain largely unknown. Building upon our
previous findings, this renewal aims to fill this knowledge gap by addressing three key questions: (1) How does Bb
control asymmetrical flagellar rotation? Due to its unique cell shape and geometry, Bb must rotate its bipolar
periplasmic flagella (PF) asymmetrically in order to run: the anterior PF rotates counterclockwise, and the posterior
PF rotates clockwise. Without asymmetrical rotation, the cells become distorted. This is a hallmark feature of
spirochete motility; however, its underlying molecular mechanism remains elusive. Aim 1 seeks to unravel this
longstanding conundrum by determining the function and structure of FliG1, a noncanonical flagellar motor switch
protein, using an integrative approach of genetics, biochemistry, cryo-electron tomography, and crystallography.
(2) Has Bb evolved swarming motility to facilitate its invasiveness and virulence? During the enzootic cycle,
on several occasions, Bb swims in highly viscous gel-like environments, such as mammalian dermis tissue and the
tick-gut basement membrane, which are reminiscent of the environments in which bacteria swarm, a form of
movement that allows bacteria to crawl over solid and semi-solid surfaces. It has been speculated that Bb has
evolved swarming motility to empower its invasiveness. Aim 2 plans to delineate the underlying mechanism of
swarming motility and its role in the pathogenicity of Bb, using a comprehensive approach of genetics, biochemistry,
structural biology, and in vivo animal models along with intravital imaging. (3) Does CheA1 control Bb virulence
and, if so, how? Bb has evolved unique chemotaxis to accommodate its distinct motility and enzootic cycle, e.g.,
its genome encodes multiple chemotaxis proteins such as two CheA histidine kinases (HK): CheA1 and CheA2. A
longstanding question is why Bb needs multiple chemotaxis proteins. CheA2, but not CheA1, is essential for Bb
chemotaxis. The role of CheA1 remains unknown. Interestingly, we recently found that CheA1 is required for Bb
hematogenous dissemination in mice and expression of several key virulence factors of Bb. Building upon these
results, Aim 3 proposes to elucidate the role and underlying molecular mechanism of CheA1 in Bb pathogenicity,
using a multidisciplinary approach of genetics, biochemistry, RNA-seq, and animal models. A...

## Key facts

- **NIH application ID:** 10761752
- **Project number:** 5R01AI078958-13
- **Recipient organization:** VIRGINIA COMMONWEALTH UNIVERSITY
- **Principal Investigator:** Chunhao Chris Li
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $473,229
- **Award type:** 5
- **Project period:** 2008-09-19 → 2027-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10761752

## Citation

> US National Institutes of Health, RePORTER application 10761752, Understanding Unique Aspects of Motility and Chemotaxis in Borrelia burgdorferi (5R01AI078958-13). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10761752. Licensed CC0.

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