Friday, July 4, 2025 7/4/2025

Mechanisms of MRSA intestinal colonization

Award Number: R01AI140754
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: 01/17/2020
PERIOD OF PERFORMANCE END DATE: 12/31/2024

Group Awards By:

View Award Description

Mechanisms of MRSA intestinal colonization - SUMMARY Our long-term objective is to find ways to control methicillin-resistant Staphylococcus aureus (MRSA). Here we focus on characterizing how community-acquired (CA)-MRSA colonizes the gastrointestinal (GI) tract. A key, but underappreciated, observation is that GI colonization establishes a reservoir for transmission and is the most common origin for CA-MRSA infection in infants and young children, who are at greater risk of infection than adults. We and others have used murine models to identify S. aureus traits that support GI colonization. However, the mechanisms governing GI colonization relevant to CA-MRSA are poorly understood, in part due to the use of animal models that rely on antibiotic depletion of gut microbiota to establish colonization. Our recent published and unpublished work adapted an infant mouse model to provide a tractable system relevant to CA-MRSA GI colonization in the community, especially among infants and children. Our preliminary data, obtained using this model, show that weaning is associated with colonization resistance to CA-MRSA. We also show that pore- forming leukotoxins (“toxins”) promote CA-MRSA colonization in weaned mice, but had no effect in infant mice or germ-free adult mice. Given our finding that weaning was associated with colonization resistance to CA- MRSA, a property thought to be conferred by commensal microbiota, we hypothesize that perturbation of commensal bacteria by toxins empowers CA-MRSA to overcome colonization resistance by commensal bacteria. We also established that colonization resistance against CA-MRSA is paradoxically increased in mice that lack adaptive immunity (B and T cells). Given that innate immune cells that shape the gut microbiota during weaning and confer resistance to pathogens are upregulated in such mice, we secondarily hypothesize that innate immunity and the microbiota combine to inhibit CA-MRSA colonization. To test our hypotheses, we will 1) identify commensal species that mediate CA-MRSA colonization resistance in the gut, 2) understand the immune mechanisms that inhibit the CA-MRSA colonization in mice without adaptive immunity, and 3) determine the specific CA-MRSA toxins and interactions between S. aureus and gut commensals that affect bacterial competition. The outcomes of these studies promise to identify bacterial taxa, innate immune mechanisms, and CA-MRSA loci we might manipulate to perturb CA-MRSA colonization. The results will guide future efforts to identify microbiota and cell-type-specific targets for rationally designed therapeutic strategies that modulate colonization. To the extent that the work identifies virulence factors that contribute directly to pathogen transmission, our work will also uncover bacterial mechanisms that could be exploited as targets for dual-action therapeutics.


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 = $696,333 )
2024	2024	NEW YORK UNIVERSITY	550 1ST AVE	NEW YORK	NY	10016	NEW YORK	USA	Allergy and Infectious Diseases Research	000	5	12/11/2023	NON-COMPETING CONTINUATION	$626,700
2024	2024	NEW YORK UNIVERSITY	550 1ST AVE	NEW YORK	NY	10016	NEW YORK	USA	Allergy and Infectious Diseases Research	001	5	5/21/2024	NON-COMPETING CONTINUATION	$69,633
														Subtotal = $696,333

Issue Date FY: 2023 ( Subtotal = $699,723 )
2023	2023	NEW YORK UNIVERSITY	550 1ST AVE	NEW YORK	NY	10016	NEW YORK	USA	Allergy and Infectious Diseases Research	000	4	12/21/2022	NON-COMPETING CONTINUATION	$699,723
2023	2023	NEW YORK UNIVERSITY	550 1ST AVE	NEW YORK	NY	10016	NEW YORK	USA	Allergy and Infectious Diseases Research	001	4	6/12/2023	NON-COMPETING CONTINUATION	$0
														Subtotal = $699,723

Issue Date FY: 2022 ( Subtotal = $699,723 )
2022	2022	NEW YORK UNIVERSITY	550 1ST AVE	NEW YORK	NY	10016	NEW YORK	USA	Allergy and Infectious Diseases Research	000	3	1/7/2022	NON-COMPETING CONTINUATION	$699,723
														Subtotal = $699,723

Issue Date FY: 2021 ( Subtotal = $699,723 )
2021	2021	NEW YORK UNIVERSITY	550 1ST AVE	NEW YORK	NY	10016	NEW YORK	USA	Allergy and Infectious Diseases Research	000	2	12/23/2020	NON-COMPETING CONTINUATION	$699,723
														Subtotal = $699,723

Issue Date FY: 2020 ( Subtotal = $699,723 )
2020	2020	NEW YORK UNIVERSITY	550 1ST AVE	NEW YORK	NY	10016	NEW YORK	USA	Allergy and Infectious Diseases Research	001	1	6/4/2020	NEW	$0
2020	2020	NEW YORK UNIVERSITY	550 1ST AVE	NEW YORK	NY	10016	NEW YORK	USA	Allergy and Infectious Diseases Research	000	1	1/17/2020	NEW	$699,723
														Subtotal = $699,723

Grand Total All Awards = $3,495,225

Top

All Categories

About

Search

Reports

Data Submission

Award Information

Mechanisms of MRSA intestinal colonization

Award Number: R01AI140754

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: 01/17/2020

PERIOD OF PERFORMANCE END DATE: 12/31/2024

Federal Websites

Department of Health & Human Services

HHS Operating Divisions

HHS Staff Divisions

Download A Document Viewer