Combating Antibiotic-Resistant Bacteria (CARB) Interdisciplinary Research Units (U19 Clinical Trial Not Allowed)
NIH - National Institutes of Health (RFA-AI-20-001)
- Proposal: 05/08/2020
- Amount: $1.5m per year
- Duration: 5 years
The objective of this FOA is to establish multi-project, multidisciplinary Combating Antibiotic-Resistant Bacteria (CARB) Interdisciplinary Research Units (CARBIRUs) focused on improving our understanding of bacterial and host factors important for antibacterial resistance and infection. It is expected that each CARBIRU will conduct coordinated research activities centered on a unifying theme or hypotheses to address important gaps in our current knowledge that will facilitate translation of discoveries into strategies to combat antibiotic-resistant bacterial infections.
This initiative is focused on bacterial pathogens for which antibiotic resistance poses a significant public health concern as designated in CDC’s report on Antibiotic Resistance Threats in the United States, 2019, except drug-resistant tuberculosis which is supported by other NIAID programs. These bacteria include the “Urgent Threats” carbapenem-resistant Acinetobacter, Clostridioides difficile, carbapenem-resistant Enterobacteriaceae (CRE), and drug-resistant Neisseria gonorrhoeae; the “Serious Threats” drug-resistant Campylobacter, extended-spectrum beta-lactamase (ESBL)-producing Enterobacteriaceae, vancomycin-resistant Enterococci (VRE), multidrug-resistant Pseudomonas aeruginosa, drug-resistant nontyphoidal Salmonella, drug-resistant Salmonella serotype Typhi, drug-resistant Shigella, methicillin-resistant Staphylococcus aureus (MRSA), drug-resistant Streptococcus pneumoniae (S. pneumoniae); and the “Concerning Threats” erythromycin-resistant Group A Streptococcus and clindamycin-resistant Group B Streptococcus; as well as drug-resistant Bordetella pertussis which is on the watch list.
The CARBIRU program is intended to support fundamental, collaborative research ranging from discovery to early development research activities such as discovery and validation of viable therapeutic, diagnostic, or vaccine targets; identification and characterization of host factors involved in susceptibility or response to infection and/or resistance; elucidation of known or evolving mechanisms of antibiotic resistance; and/or identification and development of novel approaches to combat antibiotic-resistant infections. The CARBIRU program is not intended for support of preclinical development of already well-characterized lead countermeasure candidates because these activities are supported by other NIAID programs.
NIAID anticipates considerable variety among the proposed program themes and objectives. It’s envisioned that themes could include, but are not limited to:
- Validation of novel therapeutic, diagnostic, or vaccine targets/pathways.
- Elucidation of mechanisms of antibiotic resistance and strategies to prevent the emergence of resistance.
- Understanding antibiotic treatment failure, including the contribution of non-genotypic resistance/persistence mechanisms.
- Understanding failure of certain vaccine candidates and design of new vaccine approaches.
- Understanding the role of the microbiome and antibiotic-mediated dysbiosis in the development of resistant infections.
CARBIRU projects contributing to a unifying theme could include, but are not limited to:
- Discovery and functional characterization of bacterial and host factors and pathways that are important for infection and antibacterial resistance.
- Systems-level approaches to identify host and bacterial molecular interactions important for infection and antibacterial resistance.
- Studies to improve our understanding of genotypic and phenotypic mechanisms of antibiotic resistance and their contribution to bacterial persistence.
- Discovery and validation of novel drug targets and early drug screening.
- Characterization and validation of non-antibiotic products like bacteriophage and live microbiome-based products.
- Discovery research to enable development of rapid, sensitive, and accurate diagnostics.
- Studies to improve our understanding of the host response to infection including identification of correlates of immune protection to inform vaccine, immunotherapeutic, and immunomodulatory research.
- Computational approaches to integrate data derived from multiple sources (e.g., transcriptomics, proteomics, metabolomics, electronic health records) to identify molecular (biomarker) signatures associated with protection against, and resolution of, antimicrobial resistant infections.
- Studies on human-associated microbial communities and the role they play in susceptibility or resistance to resistant infections.
Collaborative Interdisciplinary teams
The scope of this work requires establishing interdisciplinary teams capable of pursuing coordinated activities that bridge disparate scientific disciplines and expertise to address key research gaps in the field of antibacterial resistance. Bringing multidisciplinary groups together creates opportunities for synergy that would rarely happen otherwise.
Each CARBIRU is expected to include researchers with unique and diverse expertise that will enhance the overall quality of the program. Teams can be comprised of investigators with any relevant expertise needed to successfully accomplish the goals of the program such as microbiology, immunology, molecular genetics, biochemistry, structural biology, animal models, high-throughput drug screening and assay development, microbiome studies, high-throughput experimental and omics technologies, computational biology and modeling, as well as clinicians. The research teams within each program may be composed of investigators located at one institution or may be formed through a consortium of different institutions.
Eligibility & Submission Requirements
Applications proposing the following types of studies will be considered non-responsive and will not be reviewed:
- Applications not focused on bacteria designated in CDC’s report on Antibiotic Resistance Threats in the United States, 2019 (https://www.cdc.gov/drugresistance/pdf/threats-report/2019-ar-threats-report-508.pdf).
- Applications focused on mycobacteria or drug-resistant tuberculosis since they are supported by other NIAID programs.
- Applications focused on fungal pathogens.
Nancy Lewis Ernst, Ph.D.
National Institute of Allergy and Infectious Diseases (NIAID)