# Control of Flagellar Filament Length by FlaG in Polarly-Flagellated Bacterial Pathogens

> **NIH NIH R21** · UT SOUTHWESTERN MEDICAL CENTER · 2022 · $205,000

## Abstract

Project Summary
Bacteria produce various macromolecular surface organelles that function in different processes. For many
organelles, it is unclear how bacteria regulate their dimensions or even if a specific mechanism exists to
govern the size or length of the organelle. The flagellum is a surface organelle that facilitates swimming motility
and migration of pathogens to ideal niches in hosts to initiate infection and pathogenesis of disease. Two
specific mechanisms have been discovered in flagellar biogenesis that regulate the length of the periplasmic
rod and surface hook. However, a current hypothesis states that bacteria do not have a specific and active
mechanism to regulate the length of the extracellular flagellar filament, which functions as the propeller of the
flagellar motor and extends ~10 µm on the surface of model peritrichous bacteria such as Salmonella species
and E. coli. Challenging this hypothesis are observations that many polarly-flagellated bacterial pathogens,
such as Campylobacter jejuni, Vibrio cholerae, and Pseudomonas aeruginosa, produce flagellar filaments
~70% shorter than those of peritrichous bacteria. Furthermore, deletion of flaG that is conserved in these
pathogens and many other polar flagellates but absent in peritrichous organisms, caused flagellar filaments to
extend up to twice the length as those of WT cells. In addition, C. jejuni DflaG producing elongated flagellar
filaments displayed a 28-fold defect for cecal colonization of the natural avian host, suggesting that properly
regulating flagellar filament length is necessary for optimal colonization of a host. Together, these findings
indicate that FlaG in polar flagellates is involved in a specific and active mechanism to control the extracellular
length of the flagellar filament and is important for some pathogens to colonize hosts, but a molecular
mechanism for how FlaG controls filament length is unknown. In this proposal, we will use C. jejuni as a model
system for polar flagellates to understand how a bacterium employs FlaG to control the length of the flagellar
filament by halting filament polymerization, an event that occurs at a large distance (~2-3 cell body lengths)
from the bacterial surface. We will test two non-mutually exclusive hypotheses that FlaG controls flagellar
filament length by the following mechanisms: 1) FlaG interfering with interactions between the filament-building
flagellin subunits and the FliS chaperone to reduce flagellin secretion; and/or 2) FlaG functioning as a flagellin
mimic to block flagellins from polymerizing into the filament at the tip of the flagellum. We will also investigate
why production of elongated flagellar filaments by C. jejuni DflaG reduces the ability to colonize a host by
analyzing the effects of elongated filaments on motility efficiency and velocity through different physiologically-
relevant viscosities and secretion of proteins through the flagellum required for host interactions. Outcomes
from t...

## Key facts

- **NIH application ID:** 10493413
- **Project number:** 5R21AI159140-02
- **Recipient organization:** UT SOUTHWESTERN MEDICAL CENTER
- **Principal Investigator:** DAVID R HENDRIXSON
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $205,000
- **Award type:** 5
- **Project period:** 2021-09-22 → 2024-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10493413

## Citation

> US National Institutes of Health, RePORTER application 10493413, Control of Flagellar Filament Length by FlaG in Polarly-Flagellated Bacterial Pathogens (5R21AI159140-02). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10493413. Licensed CC0.

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