R01AI163161

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. Furthermore, 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.

Washington University

TO ASSIST PUBLIC AND PRIVATE NONPROFIT INSTITUTIONS AND INDIVIDUALS TO ESTABLISH, EXPAND AND IMPROVE BIOMEDICAL RESEARCH AND RESEARCH TRAINING IN INFECTIOUS DISEASES AND RELATED AREAS, TO CONDUCT DEVELOPMENTAL RESEARCH, TO PRODUCE AND TEST RESEARCH MATERIALS. TO ASSIST PUBLIC, PRIVATE AND COMMERCIAL INSTITUTIONS TO CONDUCT DEVELOPMENTAL RESEARCH, TO PRODUCE AND TEST RESEARCH MATERIALS, TO PROVIDE RESEARCH SERVICES AS REQUIRED BY THE AGENCY FOR PROGRAMS IN INFECTIOUS DISEASES, AND CONTROLLING DISEASE CAUSED BY INFECTIOUS OR PARASITIC AGENTS, ALLERGIC AND IMMUNOLOGIC DISEASES AND RELATED AREAS. PROJECTS RANGE FROM STUDIES OF MICROBIAL PHYSIOLOGY AND ANTIGENIC STRUCTURE TO COLLABORATIVE TRIALS OF EXPERIMENTAL DRUGS AND VACCINES, MECHANISMS OF RESISTANCE TO ANTIBIOTICS AS WELL AS RESEARCH DEALING WITH EPIDEMIOLOGICAL OBSERVATIONS IN HOSPITALIZED PATIENTS OR COMMUNITY POPULATIONS AND PROGRESS IN ALLERGIC AND IMMUNOLOGIC DISEASES. BECAUSE OF THIS DUAL FOCUS, THE PROGRAM ENCOMPASSES BOTH BASIC RESEARCH AND CLINICAL RESEARCH. SMALL BUSINESS INNOVATION RESEARCH (SBIR) PROGRAM EXPANDS AND IMPROVES PRIVATE SECTOR PARTICIPATION IN BIOMEDICAL RESEARCH. THE SBIR PROGRAM INTENDS TO INCREASE AND FACILITATE PRIVATE SECTOR COMMERCIALIZATION OF INNOVATIONS DERIVED FROM FEDERAL RESEARCH AND DEVELOPMENT, TO INCREASE SMALL BUSINESS PARTICIPATION IN FEDERAL RESEARCH AND DEVELOPMENT, AND TO FOSTER AND ENCOURAGE PARTICIPATION OF SOCIALLY AND ECONOMICALLY DISADVANTAGED SMALL BUSINESS CONCERNS AND WOMEN-OWNED SMALL BUSINESS CONCERNS IN TECHNOLOGICAL INNOVATION. THE SMALL BUSINESS TECHNOLOGY TRANSFER (STTR) PROGRAM STIMULATES AND FOSTERS SCIENTIFIC AND TECHNOLOGICAL INNOVATION THROUGH COOPERATIVE RESEARCH AND DEVELOPMENT CARRIED OUT BETWEEN SMALL BUSINESS CONCERNS AND RESEARCH INSTITUTIONS, TO FOSTER TECHNOLOGY TRANSFER BETWEEN SMALL BUSINESS CONCERNS AND RESEARCH INSTITUTIONS, TO INCREASE PRIVATE SECTOR COMMERCIALIZATION OF INNOVATIONS DERIVED FROM FEDERAL RESEARCH AND DEVELOPMENT, AND TO FOSTER AND ENCOURAGE PARTICIPATION OF SOCIALLY AND ECONOMICALLY DISADVANTAGED SMALL BUSINESS CONCERNS AND WOMEN-OWNED SMALL BUSINESS CONCERNS IN TECHNOLOGICAL INNOVATION. RESEARCH CAREER DEVELOPMENT AWARDS SUPPORT THE DEVELOPMENT OF SCIENTISTS DURING THE FORMATIVE STAGES OF THEIR CAREERS. INDIVIDUAL NATIONAL RESEARCH SERVICE AWARDS (NRSAS) ARE MADE DIRECTLY TO APPROVE APPLICANTS FOR RESEARCH TRAINING IN SPECIFIED BIOMEDICAL SHORTAGE AREAS. IN ADDITION, INSTITUTIONAL NATIONAL RESEARCH SERVICE AWARDS ARE MADE TO ENABLE INSTITUTIONS TO SELECT AND MAKE AWARDS TO INDIVIDUALS TO RECEIVE TRAINING UNDER THE AEGIS OF THEIR INSTITUTIONAL PROGRAM.

93.855 - Allergy and Infectious Diseases Research

National Institute of Allergy and Infectious Diseases (NIAID) [HHS - NIH]

Saint Louis, Missouri 631101010 United States

Single Zip Code

Generating New insights and Mechanistic Understanding of Antibiotic Resistance Development (R01 Clinical Trial Not Allowed) (PA-18-725)

Amendment Since initial award the End Date has been extended from 04/30/26 to 04/30/27 and the total obligations have increased 333% from $785,082 to $3,400,860.