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Microbial Community Disruption Following Topical Antimicrobial Application in Staphylococcus aureus-Affected Households

Award Number: R01AI163161
ORGANIZATION: NATIONAL INSTITUTE OF ALLERGY & INFECTIOUS DISEASES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

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Microbial Community Disruption Following Topical Antimicrobial Application in Staphylococcus aureus-Affected Households - PROJECT SUMMARY The National Action Plan for Combating Antibiotic-Resistant Bacteria identified critical research needs to confront the advancing threat of antimicrobial resistance. These include understanding the nature of microbial communities, determining the effects of antibiotics on these communities, and harnessing these communities to develop strategies for disease prevention. Staphylococcus aureus causes significant morbidity and mortality in healthcare and community settings. S. aureus carriage confers risk for endogenous infection. Previous studies investigated clinical and epidemiological factors associated with S. aureus colonization and infection, although the influence of the skin and nasal microbiota on S. aureus acquisition is unclear. We hypothesize that features of the commensal microbiota may confer susceptibility to, or provide protection against, S. aureus acquisition and development of subsequent infection. Further, in an effort to prevent S. aureus acquisition and infection, decolonization with topical antimicrobials is frequently employed in healthcare and community settings. However, broad-spectrum topical antimicrobial application may disrupt commensal microbiota, thereby promoting the acquisition or enrichment of multidrug-resistant and/or potentially pathogenic microorganisms. The impact of this potential adverse effect remains understudied. In this proposed project, we will analyze a vast and unmatched biorepository of >13,000 skin and nasal swab samples that were longitudinally collected over 24 months from a well-characterized cohort of 476 participants, including 99 pediatric patients with methicillin-resistant S. aureus skin infections and their household contacts, all of whom are at high risk for S. aureus acquisition and infection. The samples were collected during 12 months of longitudinal samplings (the natural history phase) followed by a randomized, 5-day decolonization intervention with topical antimicrobial application, and subsequent longitudinal sampling for 12 months (post-decolonization phase). We will perform metagenomic shotgun sequencing (enabling classification at the species and strain levels), to longitudinally characterize skin and nasal microbial communities in the context of S. aureus colonization and disease. We will compare microbial community features associated with susceptibility or resistance to S. aureus acquisition between household contacts with different phenotypic outcomes (e.g., colonization and infection), and integrate these data with detailed epidemiological data to predict individuals at risk for acquiring S. aureus colonization and/or developing symptomatic infection. We will quantify changes in microbial community structures following topical antimicrobial application, and correlate this disruption with subsequent acquisition and persistence of S. aureus and other pathogens. Finally, we will employ innovative targeted sequence capture to quantify genetic determinants of antimicrobial resistance (the “resistome”) in samples collected before and after decolonization. The essential knowledge generated by this study will optimize preventive strategies for S. aureus colonization and infection and their targeting to susceptible individuals.


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 = $775,632 )
2025	2025	WASHINGTON UNIVERSITY, THE	1 BROOKINGS DR	SAINT LOUIS	MO	63130	SAINT LOUIS	USA	Allergy and Infectious Diseases Research	000	5	3/28/2025	NON-COMPETING CONTINUATION	$775,632
														Subtotal = $775,632

Issue Date FY: 2024 ( Subtotal = $278,644 )
2024	2024	WASHINGTON UNIVERSITY, THE	ONE BROOKINGS DR	SAINT LOUIS	MO	63110	SAINT LOUIS CITY	USA	Allergy and Infectious Diseases Research	000	4	5/22/2024	NON-COMPETING CONTINUATION	$278,644
														Subtotal = $278,644

Issue Date FY: 2023 ( Subtotal = $779,570 )
2023	2023	WASHINGTON UNIVERSITY, THE	ONE BROOKINGS DR	SAINT LOUIS	MO	63130	SAINT LOUIS	USA	Allergy and Infectious Diseases Research	000	3	4/10/2023	NON-COMPETING CONTINUATION	$779,570
														Subtotal = $779,570

Issue Date FY: 2022 ( Subtotal = $781,932 )
2022	2022	WASHINGTON UNIVERSITY, THE	ONE BROOKINGS DR	SAINT LOUIS	MO	63130	SAINT LOUIS	USA	Allergy and Infectious Diseases Research	001	2	4/12/2022	NON-COMPETING CONTINUATION	$781,932
2022	2021	WASHINGTON UNIVERSITY, THE	ONE BROOKINGS DR	SAINT LOUIS	MO	63130	SAINT LOUIS	USA	Allergy and Infectious Diseases Research	000	1	10/13/2021	NEW	$0
														Subtotal = $781,932

Issue Date FY: 2021 ( Subtotal = $785,082 )
2021	2021	WASHINGTON UNIVERSITY, THE	ONE BROOKINGS DR	SAINT LOUIS	MO	63130	SAINT LOUIS	USA	Allergy and Infectious Diseases Research	000	1	5/19/2021	NEW	$785,082
														Subtotal = $785,082

Grand Total All Awards = $3,400,860

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Microbial Community Disruption Following Topical Antimicrobial Application in Staphylococcus aureus-Affected Households

Award Number: R01AI163161

ORGANIZATION: NATIONAL INSTITUTE OF ALLERGY & INFECTIOUS DISEASES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

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