# Mechanical Regulation of Chemotaxis Signaling by Bacterial Mechanosensors

> **NIH NIH R01** · TEXAS ENGINEERING EXPERIMENT STATION · 2024 · $348,950

## Abstract

Project Abstract
 Bacterial infections and chronic diseases cause significant healthcare costs each year. However, the
mechanisms underlying the formation of bacterial communities, such as biofilms and swarming colonies, remain
poorly understood. Community formation by motile bacteria is typically initiated when a cell senses its attachment
to a surface, usually by utilizing the flagellum as a tactile (mechanosensor) sensor. The flagellar stator, which
rotates the flagellum, has been shown to sense mechanical obstruction upon adhesion to a surface and remodel
in response. The remodeled stator delivers higher mechanical force to rotate the flagellar rotor. While the stator
has been widely implicated in surface sensing and biochemical signaling, the mechanisms are not understood.
Understanding these mechanisms is critical for developing innovative strategies to prevent bacterial community
formation. The PI's preliminary findings have uncovered a link between chemotaxis signaling and stator
mechanosensing. Therefore, the objective of the proposed work is to explain the mechanistic basis for this link
and reveal fundamental insights into mechanotransduction in bacteria. The long-term goal is to develop clinically
useful strategies to prevent chronic bacterial infections and antibiotic resistance. The proposed projects will
quantitatively measure the mechanical stimuli on the flagella as the cell's extracellular environment changes.
Investigations will determine the correlation between mechanical stimuli and the stator's role in maintaining
homeostasis in the output of the chemotaxis signaling network, which enables the cell to transition to surface-
adapted lifestyles. The mechanism by which the stator amplifies force delivered to the rotor to adapt the
chemotactic output will be determined to explain the basis for its mechanosensitive functions. Finally, the
mechanism by which the cell globally couples mechanosensitive flagellar functions will be explained. The
proposed work will employ advanced biophysical techniques such as optical tweezers, single-motor mechanical
stimulation assays, single-molecule fluorescence measurements, molecular biology tools, and stochastic
modeling. It is expected that the results will help establish a paradigm for understanding how bacteria integrate
signals from mechanosensors to target suitable niches. Quantification of the extracellular mechanical stimuli
typically encountered by the cells is anticipated to assist researchers in interpreting motility results across diverse
bacterial species.

## Key facts

- **NIH application ID:** 10804223
- **Project number:** 2R01GM123085-05A1
- **Recipient organization:** TEXAS ENGINEERING EXPERIMENT STATION
- **Principal Investigator:** Pushkar Prakash Lele
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $348,950
- **Award type:** 2
- **Project period:** 2017-09-15 → 2026-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10804223

## Citation

> US National Institutes of Health, RePORTER application 10804223, Mechanical Regulation of Chemotaxis Signaling by Bacterial Mechanosensors (2R01GM123085-05A1). Retrieved via AI Analytics 2026-05-28 from https://api.ai-analytics.org/grant/nih/10804223. Licensed CC0.

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