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Mechanical Regulation of Chemotaxis Signaling by Bacterial Mechanosensors

Award Number: R01GM123085
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: 09/15/2017
PERIOD OF PERFORMANCE END DATE: 08/31/2026

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Mechanical Regulation of Chemotaxis Signaling by Bacterial Mechanosensors - 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.


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: 2025 ( Subtotal = $313,793 )
2025	2025	TEXAS A&M ENGINEERING EXPERIMENT STATION	3124 TAMU	COLLEGE STATION	TX	77843	BRAZOS	USA	Biomedical Research and Research Training	000	6	8/8/2025	NON-COMPETING CONTINUATION	$313,793
														Subtotal = $313,793

Issue Date FY: 2024 ( Subtotal = $348,950 )
2024	2024	TEXAS A&M ENGINEERING EXPERIMENT STATION	3124 TAMU	COLLEGE STATION	TX	77843	BRAZOS	USA	Biomedical Research and Research Training	000	5	8/6/2024	COMPETING CONTINUATION	$348,950
														Subtotal = $348,950

Issue Date FY: 2023 ( Subtotal = -$418 )
2023	2020	TEXAS A&M ENGINEERING EXPERIMENT STATION	3124 TAMU	COLLEGE STATION	TX	77843	BRAZOS	USA	Biomedical Research and Research Training	000	4	6/13/2023	NON-COMPETING CONTINUATION	-$418
														Subtotal = -$418

Issue Date FY: 2020 ( Subtotal = $282,460 )
2020	2020	TEXAS A&M ENGINEERING EXPERIMENT STATION	7607 EASTMARK DR	COLLEGE STATION	TX	77840	BRAZOS	USA	Biomedical Research and Research Training	000	4	8/24/2020	NON-COMPETING CONTINUATION	$282,460
														Subtotal = $282,460

Issue Date FY: 2019 ( Subtotal = $283,267 )
2019	2019	TEXAS A&M ENGINEERING EXPERIMENT STATION	7607 EASTMARK DR	COLLEGE STATION	TX	77840	BRAZOS	USA	Biomedical Research and Research Training	000	3	8/26/2019	NON-COMPETING CONTINUATION	$283,267
														Subtotal = $283,267

Issue Date FY: 2018 ( Subtotal = $335,003 )
2018	2018	TEXAS A&M ENGINEERING EXPERIMENT STATION	7607 EASTMARK DR	COLLEGE STATION	TX	77840	BRAZOS	USA	Biomedical Research and Research Training	000	2	9/3/2018	NON-COMPETING CONTINUATION	$254,805
2018	2018	TEXAS A&M ENGINEERING EXPERIMENT STATION	7607 EASTMARK DR	COLLEGE STATION	TX	77840	BRAZOS	USA	Biomedical Research and Research Training	001	2	9/19/2018	SUPPLEMENT FOR EXPANSION	$80,198
														Subtotal = $335,003

Issue Date FY: 2017 ( Subtotal = $255,161 )
2017	2017	TEXAS A&M ENGINEERING EXPERIMENT STATION	7607 EASTMARK DR	COLLEGE STATION	TX	77840	BRAZOS	USA	Biomedical Research and Research Training	000	1	9/14/2017	NEW	$255,161
														Subtotal = $255,161

Grand Total All Awards = $1,818,216

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Mechanical Regulation of Chemotaxis Signaling by Bacterial Mechanosensors

Award Number: R01GM123085

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: 09/15/2017

PERIOD OF PERFORMANCE END DATE: 08/31/2026

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