# Biophysical Determinants of Chemotaxis in Helicobacter Pylori

> **NIH NIH R01** · TEXAS ENGINEERING EXPERIMENT STATION · 2024 · $172,209

## Abstract

Project Abstract
 Infections by the motile bacterial species, Helicobacter pylori, are promoted by
chemotaxis, which refers to the ability to migrate towards favorable chemical environments. H.
pylori infections are a major cause of peptic ulcers and gastric cancers. Yet, the biophysical
mechanisms of chemotaxis in H. pylori are not understood. In the canonical chemotaxis network,
chemoreceptors sense extracellular ligands and regulate the activity of a chemotaxis kinase. The
kinase in turn modulates flagellar functions to bias bacterial migration. To prevent the network
from desensitizing upon ligand-detection, two enzymes, CheR and CheB, continuously reset the
kinase activity. Such resetting (adaptation) increases the dynamic range of ligand sensing in the
network, without which the cell cannot continue migrating up or down chemical gradients.
However, H. pylori lack CheR and CheB homologues. Also, the pattern of motility in H. pylori is
different from the standard model, Escherichia coli, since H. pylori localize all their flagella at a
single pole – individual cells swim forward (run) and backward (reverse), rather than running and
tumbling as E. coli do. This subtle difference in motility is predicted to give rise to multiple
chemotaxis errors in the canonical framework. Hence, current mechanistic models of chemotaxis
are unable to explain biased and error-free migration in H. pylori. Without a fundamental
understanding of chemotaxis in H. pylori, the development of antibacterials that target chemotaxis
will likely remain limited. In the proposed work, the PI’s primary goal is to explain how the
chemotaxis network modulates flagellar functions to promote chemotaxis in H. pylori. The PI’s
long term goal is to use the insights from the proposed work to develop innovative methods to
prevent H. pylori infections by inhibiting chemotaxis. The PI will make use of a novel technique
that overcomes the status quo by allowing quantification of flagellar functions without probing
individual flagellar motors. Through a combination of optical tweezers, phase microscopy, and
stochastic modeling, the PI will determine how chemotaxis errors are prevented at a single cell
and population level in H. pylori. The team will pioneer the development of novel assays, including
a FRET assay, to experimentally measure chemotaxis signaling in H. pylori. The PI will also
determine the role of key coupling proteins that have been hypothesized to play a major role in
chemotaxis adaptation. In addition to establishing the biophysical principles of chemotaxis in H.
pylori, the following payoffs are anticipated: 1) a paradigm will be established for understanding
chemotaxis migration in other run-reversing species, 2) novel mechanisms of chemotaxis
adaptation are likely to be elucidated, 3. a FRET-based assay will be developed, which will
significantly boost current efforts in the field to understand chemoreceptor functions and
chemotaxis signaling mechanisms in H. pylori. ...

## Key facts

- **NIH application ID:** 11081496
- **Project number:** 3R01GM141690-03S1
- **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:** $172,209
- **Award type:** 3
- **Project period:** 2022-02-01 → 2026-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/11081496

## Citation

> US National Institutes of Health, RePORTER application 11081496, Biophysical Determinants of Chemotaxis in Helicobacter Pylori (3R01GM141690-03S1). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/11081496. Licensed CC0.

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