Wednesday, July 2, 2025 7/2/2025

Investigation of gut microbiota metabolite-mediated transkingdom interactions with fungi

Award Number: R01AI178683
ORGANIZATION: NATIONAL INSTITUTE OF ALLERGY & INFECTIOUS DISEASES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 03/01/2024
PERIOD OF PERFORMANCE END DATE: 01/31/2029

Group Awards By:

View Award Description

Investigation of gut microbiota metabolite-mediated transkingdom interactions with fungi - Project Summary The human intestinal tract supports a complex microbial environment consisting of bacterial (or microbiota) and fungal (or mycobiota) constituents. Although the role of each of these communities has been a subject of multiple studies, the role of transkingdom interactions between fungi and bacteria in shaping host immunity and physiology has been much less explored. The chemical basis for such interactions, critical for the rational design of mechanistic studies with regards to host immunity and disease development, remain completely uncharted territory in the literature. We have established a genetic manipulation pipeline to identify gene transfer methodology and build a genetic tool for nonmodel human gut bacteria on a large scale. Via a multifactorial optimization of their conjugation/transformation conditions and targeting bacterial conserved 16s rRNA genes, this pipeline efficiently identified the gene transfer methods for multiple nonmodel gut bacterial commensals and set up CRISPR-based or gene insertion tools in multiple of them. This library of genetically targetable microbes comes from 5 different phyla. This genetic manipulation pipeline and this library of tractable commensals will facilitate our investigation of trans-kingdom microbiota-mycobiota interactions at the molecular level. A high throughput screening of bacterial metabolite libraries from gut bacteria identified metabolites with direct effect on intestinal mycobiota. We identified bacterial species and corresponding gene clusters responsible for the production of these metabolites. Our preliminary data suggest strong ties and specific molecular interactions between fungi and bacteria in the gut that have previously unappreciated role in microbial dynamics, metabolite production and immunity. We will utilize such bacterial strains and isogenic mutants in key biosynthetic pathways to target metabolites with mycobiota modulatory properties. We will use several mouse models and synthetic microbial communities to define the role of trans kingdom interaction between bacteria and fungi in modulating host immunity and colonization resistance in the gut. We hypothesize that metabolites from the human bacterial microbiota modulate the fungal communities in the gut to affect microbial composition, the microbiome function and immunity. In addition to revealing novel mechanisms of fungal-bacterial interaction at an unprecedented small molecule level, the results of this proposed investigation will illuminate potential new strategies for targeting of fungal pathogens


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 = $804,124 )
2025	2025	WEILL MEDICAL COLLEGE OF CORNELL UNIVERSITY	575 LEXINGTON AVE FL 9	NEW YORK	NY	10022	NEW YORK	USA	Allergy and Infectious Diseases Research	000	2	1/7/2025	NON-COMPETING CONTINUATION	$804,124
														Subtotal = $804,124

Issue Date FY: 2024 ( Subtotal = $828,994 )
2024	2024	WEILL MEDICAL COLLEGE OF CORNELL UNIVERSITY	575 LEXINGTON AVE FL 9	NEW YORK	NY	10022	NEW YORK	USA	Allergy and Infectious Diseases Research	001	1	9/4/2024	NEW	$82,899
2024	2024	WEILL MEDICAL COLLEGE OF CORNELL UNIVERSITY	575 LEXINGTON AVE FL 9	NEW YORK	NY	10022	NEW YORK	USA	Allergy and Infectious Diseases Research	000	1	3/1/2024	NEW	$746,095
														Subtotal = $828,994

Grand Total All Awards = $1,633,118

Top

All Categories

About

Search

Reports

Data Submission

Award Information

Investigation of gut microbiota metabolite-mediated transkingdom interactions with fungi

Award Number: R01AI178683

ORGANIZATION: NATIONAL INSTITUTE OF ALLERGY & INFECTIOUS DISEASES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 03/01/2024

PERIOD OF PERFORMANCE END DATE: 01/31/2029

Federal Websites

Department of Health & Human Services

HHS Operating Divisions

HHS Staff Divisions

Download A Document Viewer