# Elucidating a novel flagellar architecture from the pathogenic spirochete Leptospira and its role in motility

> **NIH NIH R56** · YALE UNIVERSITY · 2020 · $565,500

## Abstract

PROJECT SUMMARY:
The spirochetes are a group of bacteria that are responsible for several deadly ailments including the notorious
illnesses, Lyme disease and syphilis. These organisms have developed a special mode of propulsion, whereby
their flagella wrap around the cell body to power a screw-like `drilling' motion made by the entire organism. This
trait is especially useful for infecting people and other animal hosts, for two reasons: (1) it keeps the flagellum
close to the cell body, where it can be covered up by the bacterial outer membrane; this helps spirochetes
evade the host immune system, which usually recognizes flagella with ease as a `foreign invader'; and (2) the
`drilling' action is highly effective at penetrating dense materials, such as host tissue, which speeds up and
otherwise facilitates infection.
Despite the clear relevance for disease, many aspects of spirochete motility remain mysterious, including the
precise composition and three-dimensional structure of the molecular machinery that drives it. We formed a
multidisciplinary, multinational team focused on understanding the detailed structure and function of a
spirochete flagellum, working with a pathogenic strain called Leptospira that causes a deadly water-borne
illness called leptospirosis. We are using an integrative approach that combines advanced cryo-electron
microscopy and cryo-electron tomography, X-ray crystallography, molecular microbiology and genetics
techniques, to address major open questions, including: (1) why do spirochete flagella contain many distinct
types of protein components when their counterparts from other bacteria need only one; (2) what is the
molecular basis of a distinctive, highly coiled flagellar morphology in Leptospira ; and (3) how do these features
facilitate motility? By combining complementary top-down and bottom-up strategies, our approach should shed
light on spirochetal biology and pathogenesis, and unveil novel molecular targets to develop drugs and
vaccines with improved efficacy.
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## Key facts

- **NIH application ID:** 10238574
- **Project number:** 1R56AI145326-01A1
- **Recipient organization:** YALE UNIVERSITY
- **Principal Investigator:** Albert Icksang Ko
- **Activity code:** R56 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $565,500
- **Award type:** 1
- **Project period:** 2020-09-01 → 2022-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10238574

## Citation

> US National Institutes of Health, RePORTER application 10238574, Elucidating a novel flagellar architecture from the pathogenic spirochete Leptospira and its role in motility (1R56AI145326-01A1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10238574. Licensed CC0.

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