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Nutrient-driven bacterial physiology in recalcitrant infections.

Award Number: R35GM155575
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: 07/15/2024
PERIOD OF PERFORMANCE END DATE: 06/30/2029

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Nutrient-driven bacterial physiology in recalcitrant infections. - Project Summary We currently lack effective therapies for treating chronic infections because most antibiotics were screened for their ability to kill fast-growing, planktonic bacteria. In chronic infections, bacteria are difficult to eradicate because they grow slowly and form biofilms; these physiologies facilitate antibiotic tolerance and resistance to host immune defenses. Our research aims to address this challenge by investigating how the host nutrient environment drives bacteria to adopt these recalcitrant states. Our preliminary studies have identified nutrient availability as a key regulator of the slow growth and biofilm lifestyles, highlighting bacterial metabolism and the host nutrient environment as inroads for controlling these difficult-to-treat states. This research program will build from these findings to determine how nutrient cues direct the physiologies of gram-positive anaerobic cocci (GPAC). GPAC are a diverse group of obligate anaerobic bacteria; their physiologies are distinct from well-studied biofilm-forming bacteria, providing an opportunity to uncover new mechanisms for counteracting antibiotic tolerance and disrupting biofilms. GPAC are prevalent members of the human microbiota and understudied agents of chronic infections. In this proposal, we will determine how the nutrient environment supports or limits GPAC metabolism, investigating how this relationship underpins antibiotic treatment failure. We will also identify how specific nutrient cues regulate biofilm formation or dispersal, and further explore how biofilm regulation has diverged within an important GPAC lineage. Our work integrates a range of techniques to pursue mechanistic studies of GPAC physiology, including quantitative microscopy, experimental evolution, and genetic and omics approaches. We have also developed crucial new tools for studying these non-model bacteria, including genetic manipulation, defined media for manipulating the nutrient environment, and the establishment of an ex vivo wound tissue growth medium to recapitulate the host nutrient environment. In completing these projects, we will reveal how the host nutrient environment regulates bacterial physiologies that enable chronic colonization and recalcitrance to antibiotic therapies. Studying physiologically relevant bacterial states will inspire new therapeutic approaches for combatting chronic infections.


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 = $368,774 )
2026	2026	UNIVERSITY OF OREGON	1776 E 13TH AVE	EUGENE	OR	97403	LANE	USA	Biomedical Research and Research Training	000	3	6/23/2026	NON-COMPETING CONTINUATION	$368,774
														Subtotal = $368,774

Issue Date FY: 2025 ( Subtotal = $368,774 )
2025	2025	UNIVERSITY OF OREGON	1776 E 13TH AVE	EUGENE	OR	97403	LANE	USA	Biomedical Research and Research Training	000	2	6/17/2025	NON-COMPETING CONTINUATION	$368,774
														Subtotal = $368,774

Issue Date FY: 2024 ( Subtotal = $368,774 )
2024	2024	UNIVERSITY OF OREGON	1776 E 13TH AVE	EUGENE	OR	97403	LANE	USA	Biomedical Research and Research Training	000	1	7/12/2024	NEW	$368,774
														Subtotal = $368,774

Grand Total All Awards = $1,106,322

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Nutrient-driven bacterial physiology in recalcitrant infections.

Award Number: R35GM155575

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: 07/15/2024

PERIOD OF PERFORMANCE END DATE: 06/30/2029

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