U19AI157981

Microbiome Discovery and Mechanisms to Combat Antibiotic Resistance at Mucosal Surfaces - Overall Project Summary

The ability to control bacterial infections with antibiotics has been one of the most important public health advancements in human history. Before the discovery of antibiotics and vaccines, infectious disease was the leading cause of death and constituted nearly 50% of deaths in the US alone. Now, infectious diseases as a cause of death barely make the top ten, and we now treat most bacterial infections as a nuisance rather than life-threatening diseases. Unfortunately, this is rapidly changing with the emergence of antibiotic-resistant bacterial pathogens.

Ultimately, our ability to develop new antibiotics faster than resistance amongst pathogens emerges has failed, and many scientists expect we will experience a return to a pre-antibiotic era in which we cannot treat what are now easy to cure bacterial infections. Therefore, novel, non-antibiotic approaches to controlling bacterial infections are required and need to be explored.

The main theme of the BCM-CARBIRU is to use microbiome-based approaches to control bacterial infections at mucosal surfaces. We will investigate ecological principles of microbial community inhibition of pathogen colonization, as well as the use of bacteriophage for precision elimination of bacterial pathogens. Both approaches have advantages over the use of antibiotics in that they leave the native microbiome largely intact, avoiding the elimination of beneficial microbes along with the pathogens targeted by antimicrobials.

We propose three projects, supported by two scientific cores and the administrative core, to explore and optimize microbiome-based strategies for the prevention and treatment of bacterial infections.

Project 1: Discovery and Mechanistic Understanding of Phage Activity and Synergism at Host Mucosal Surfaces.

Project 2: Defined Microbial Communities to Prevent and Eradicate Infection by Antibiotic-Resistant Pathogens.

Project 3: Nasal Microbial Consortia Combat Antibiotic-Resistant Bacteria.

We expect two main outcomes from the execution of these projects. First, we expect to define and understand the ecological principles that are key for microbial communities and bacteriophage to function to control pathogens at mucosal surfaces. Second, we expect to have identified actionable phage and microbial communities that will be available for testing in human clinical trials at the end of the project periods.

Together, these projects will capitalize on protective measures at the mucosal surface, which have existed for millennia prior to modern medicine, as we enter the next era of microbiome-based therapies.

Baylor College Of Medicine

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]

Houston, Texas 770303411 United States

Single Zip Code

Combating Antibiotic-Resistant Bacteria (CARB) Interdisciplinary Research Units (U19 Clinical Trial Not Allowed) (RFA-AI-20-001)

Amendment Since initial award the total obligations have increased 420% from $2,390,117 to $12,426,743.