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Genetic analysis of competition dependent fitness determinants in the human gut bacterium Phocaeicola vulgatus

Award Number: F31AI181537
ORGANIZATION: NATIONAL INSTITUTE OF ALLERGY & INFECTIOUS DISEASES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: FELLOWSHIP/SCHOLARSHIP/STUDENT LOANS

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ABSTRACT The mammalian gut harbors complex communities of microbes that interact and compete with each other while also influencing the physiology of the host. Discerning the mechanisms by which major members of these microbial communities colonize the gut is a fundamentally important research goal. One major member is the gut bacterium Phocaeicola vulgatus (Pvu), a gram-negative anaerobe and one of the most abundant bacterial species found in the gut of humans and other mammals. Pvu has been associated with inflammatory bowel disease and several metabolic disorders, and can also infiltrate and colonize established gut microbial communities following a single introduction. However, there is a gap in understanding of the molecular tools that Pvu deploys to colonize and invade established niches in the gut. Our long-term goal is to understand what makes Pvu such an unusually efficient colonizer of the mammalian gut. Our preliminary studies have identified an operon specific to the Phocaeicola genus that is required for fitness within the mouse gut in a manner strongly dependent on microbial competition, but the specific functions of the genes in that operon remain unknown. I will address this gap by defining the requirement for the genes in this operon on Pvu physiology in vitro and on in vivo gut colonization amidst competition with other microbes. This will be accomplished through in vitro studies involving tagging proteins encoded in the operon for immunohistochemistry, lipid binding assays, and chromatin immunoprecipitation sequencing. Additionally, in vivo studies using germ-free and specific-pathogen free mice will be performed to understand how the specific genes in the operon influence Pvu's colonization efficiency and biogeography in the gut. The expected outcomes of these studies include identification of new mechanisms used by Pvu to effectively colonize the mammalian gut as well as fundamental new insights into Pvu physiology. These results will vertically advance the field by providing new understanding of Pvu's colonization strategies which could eventually lead to the development of new probiotic platforms and strategies for controlling gut microbiome composition in the context of inflammatory bowel diseases and metabolic disorders.


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: 2024 ( Subtotal = $40,502 )
2024	2024	DUKE UNIVERSITY	2200 W MAIN ST	DURHAM	NC	27705	DURHAM	USA	Allergy and Infectious Diseases Research	000	1	3/13/2024	NEW	$40,502
2024	2024	DUKE UNIVERSITY	2200 W MAIN ST	DURHAM	NC	27705	DURHAM	USA	Allergy and Infectious Diseases Research	001	1	3/13/2024	NEW	$0
														Subtotal = $40,502

Grand Total All Awards = $40,502

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Genetic analysis of competition dependent fitness determinants in the human gut bacterium Phocaeicola vulgatus

Award Number: F31AI181537

ORGANIZATION: NATIONAL INSTITUTE OF ALLERGY & INFECTIOUS DISEASES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: FELLOWSHIP/SCHOLARSHIP/STUDENT LOANS

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