# Flagellar Motor Biogenesis in Polarly-Flagellated Bacterial Pathogens

> **NIH NIH R01** · UT SOUTHWESTERN MEDICAL CENTER · 2021 · $552,587

## Abstract

Project Summary
Bacterial flagella function as two machines: a type III secretion system (T3SS) that secretes most of the
extracytoplasmic components of the flagellum and a reversible rotary motor that promotes swimming motility
required for many bacteria pathogens to infect hosts to promote disease. Peritrichous flagellates such as E.
coli and Salmonella species have served as models to understand various processes for flagellar biogenesis
and function. However, many significant bacterial pathogens, including Campylobacter jejuni, Vibrio cholerae,
Helicobacter pylori, and Pseudomonas aeruginosa are polar flagellates that produce flagellar motors in limited
numbers only at polar regions. These polar flagellar motors are characteristically more structurally complex
than their peritrichous counterparts. By using C. jejuni as a model system to understand polar flagellar motor
biogenesis and function in bacterial pathogens, we found that the increased structural complexity in polar
flagellar motors is due to both unique structures and conserved substructures formed by a different collection
of proteins. Importantly, these structural alterations enhance mechanical functions of both the C. jejuni flagellar
T3SS and the rotary motor. We discovered that the C. jejuni flagellar T3SS has an enhanced ability to secrete
flagellar proteins and assemble flagella even when lacking components usually essential for other T3SSs to
function. Furthermore, we discovered the structural alterations in the C. jejuni flagellum contribute to a common
feature of polar flagellar motors of many pathogens – the generation of higher torque for high motility velocities
in a range of physiological viscosities. We also identified C. jejuni flagellar T3SS and motor components that
promote its ability to multitask in cellular activities beyond motility. The major goal of this proposal is to analyze
how these specific structures and substructures form and adapt the C. jejuni flagellum with enhanced
mechanics to augment its function as a secretory machine and rotary motor. In Aim 1, we will analyze the
composition and arrangement of proteins forming the C. jejuni flagellar T3SS and determine how fueling
mechanics are altered relative to other T3SSs to allow it to secrete proteins and assemble flagella even without
usually essential parts. In Aim 2, we will analyze how novel disk structures form and how the rotor component
of the motor has expanded to affect the number and placement of stator units required to generate high torque
for flagellar rotation and a high velocity of motility. In Aim 3, we will explore two C. jejuni proteins that we
hypothesize function as a unique molecular brake or clutch to control output of a high-torque polar flagellar
motor and regulate optimal motility velocities in different viscosities. Completion of these aims will provide new
insights into many bacterial pathogens for: 1) how T3SSs can alter and ensure fueling to enhance secretory
activity and orga...

## Key facts

- **NIH application ID:** 10209732
- **Project number:** 2R01AI065539-16
- **Recipient organization:** UT SOUTHWESTERN MEDICAL CENTER
- **Principal Investigator:** DAVID R HENDRIXSON
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $552,587
- **Award type:** 2
- **Project period:** 2006-02-15 → 2026-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10209732

## Citation

> US National Institutes of Health, RePORTER application 10209732, Flagellar Motor Biogenesis in Polarly-Flagellated Bacterial Pathogens (2R01AI065539-16). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10209732. Licensed CC0.

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