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Biophysical determinants of chemotaxis in Helicobacter pylori

Award Number: R01GM141690
ORGANIZATION: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 02/01/2022
PERIOD OF PERFORMANCE END DATE: 01/31/2027

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Biophysical determinants of chemotaxis in Helicobacter pylori - 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. Successful execution of the projects will enable a major advance since chemotaxis strategies remain poorly understood in a large majority of bacterial species.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2026 ( Subtotal = $0 )
2026	2025	TEXAS A&M ENGINEERING EXPERIMENT STATION	3124 TAMU	COLLEGE STATION	TX	77843	BRAZOS	USA	Biomedical Research and Research Training	000	4	11/20/2025	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2025 ( Subtotal = $281,320 )
2025	2025	TEXAS A&M ENGINEERING EXPERIMENT STATION	3124 TAMU	COLLEGE STATION	TX	77843	BRAZOS	USA	Biomedical Research and Research Training	000	4	2/24/2025	NON-COMPETING CONTINUATION	$253,188
2025	2025	TEXAS A&M ENGINEERING EXPERIMENT STATION	3124 TAMU	COLLEGE STATION	TX	77843	BRAZOS	USA	Biomedical Research and Research Training	001	4	8/8/2025	NON-COMPETING CONTINUATION	$28,132
														Subtotal = $281,320

Issue Date FY: 2024 ( Subtotal = $453,529 )
2024	2024	TEXAS A&M ENGINEERING EXPERIMENT STATION	3124 TAMU	COLLEGE STATION	TX	77843	BRAZOS	USA	Biomedical Research and Research Training	001	3	6/18/2024	NON-COMPETING CONTINUATION	$28,132
2024	2024	TEXAS A&M ENGINEERING EXPERIMENT STATION	3124 TAMU	COLLEGE STATION	TX	77843	BRAZOS	USA	Biomedical Research and Research Training	000	3	1/25/2024	NON-COMPETING CONTINUATION	$253,188
2024	2024	TEXAS A&M ENGINEERING EXPERIMENT STATION	3124 TAMU	COLLEGE STATION	TX	77843	BRAZOS	USA	Biomedical Research and Research Training	002	3	9/3/2024	SUPPLEMENT FOR EXPANSION	$172,209
														Subtotal = $453,529

Issue Date FY: 2023 ( Subtotal = $525,420 )
2023	2023	TEXAS A&M ENGINEERING EXPERIMENT STATION	3124 TAMU	COLLEGE STATION	TX	77843	BRAZOS	USA	Biomedical Research and Research Training	000	2	1/9/2023	NON-COMPETING CONTINUATION	$332,017
2023	2023	TEXAS A&M ENGINEERING EXPERIMENT STATION	3124 TAMU	COLLEGE STATION	TX	77843	BRAZOS	USA	Biomedical Research and Research Training	002	2	7/11/2023	SUPPLEMENT FOR EXPANSION	$156,514
2023	2023	TEXAS A&M ENGINEERING EXPERIMENT STATION	3124 TAMU	COLLEGE STATION	TX	77843	BRAZOS	USA	Biomedical Research and Research Training	001	2	2/21/2023	NON-COMPETING CONTINUATION	$36,889
														Subtotal = $525,420

Issue Date FY: 2022 ( Subtotal = $380,863 )
2022	2022	TEXAS A&M ENGINEERING EXPERIMENT STATION	7607 EASTMARK DR	COLLEGE STATION	TX	77840	BRAZOS	USA	Biomedical Research and Research Training	000	1	1/26/2022	NEW	$380,863
														Subtotal = $380,863

Grand Total All Awards = $1,641,132

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Biophysical determinants of chemotaxis in Helicobacter pylori

Award Number: R01GM141690

ORGANIZATION: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

PERIOD OF PERFORMANCE START DATE: 02/01/2022

PERIOD OF PERFORMANCE END DATE: 01/31/2027

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