# Structure-Function Relationships in the Spirochetal Flagellar Motor

> **NIH NIH R01** · YALE UNIVERSITY · 2023 · $566,075

## Abstract

ABSTRACT
Spirochetes are a phylogenetically distinct group of bacteria that are of significant importance in human health
as they cause major diseases such as syphilis (Treponema pallidum), Lyme disease (Borrelia burgdorferi),
leptospirosis (Leptospira interrogans), and periodontitis (Treponema spp.). To infect and disseminate in
mammalian hosts, spirochetes have evolved a unique morphology and motility that is highly effective at
translocating through viscous media and tissue barriers. The organelles essential for spirochetal motility
are periplasmic flagella, which reside in the bacterial periplasmic space and are distinct from the external
flagella in the model systems Escherichia coli and Salmonella enterica. Given that flagella-driven motility is
crucial for virulence of pathogenic spirochetes and many other bacteria, our long-term goal is to understand
molecular mechanisms underlying flagellar assembly and function. During the previous funding period, we have
demonstrated that the Lyme disease spirochete B. burgdorferi (Bb) is a great model system for characterizing
periplasmic flagella in situ at an unprecedented resolution. In collaboration with Drs. Md Motaleb and Chunhao
Li, we have generated and characterized a large Bb library including 60 different flagellar and chemotaxis
mutants. Significant progress has been made in understanding the periplasmic flagella and their remarkable
capacity in driving the unique spirochetal motility and morphology. The objective of this application is to illuminate
three fundamental but challenging aspects of the periplasmic flagella: 1) the structure and function of the flagellar
type III secretion apparatus; 2) the mechanism underlying the flagellar rotation driven by proton motive force
across membrane; and 3) the mechanisms by which flagella switch rotational directions to control the motility
and chemotaxis. Together with genetic and biochemical approaches, cryo-ET will be utilized to determine the
structure/function relationship of the spirochetal flagellar motor in a native cellular environment at nanometer
resolution.

## Key facts

- **NIH application ID:** 10620656
- **Project number:** 5R01AI087946-14
- **Recipient organization:** YALE UNIVERSITY
- **Principal Investigator:** Jun Liu
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $566,075
- **Award type:** 5
- **Project period:** 2010-02-15 → 2026-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10620656

## Citation

> US National Institutes of Health, RePORTER application 10620656, Structure-Function Relationships in the Spirochetal Flagellar Motor (5R01AI087946-14). Retrieved via AI Analytics 2026-05-21 from https://api.ai-analytics.org/grant/nih/10620656. Licensed CC0.

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