Partnerships for the Development of Tools to Advance Therapeutic Discovery for Select Antimicrobial-Resistant Gram-Negative Bacteria (R01) | RFA AI 16 081

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Partnerships for the Development of Tools to Advance Therapeutic Discovery for Select Antimicrobial-Resistant Gram-Negative Bacteria (R01) is a National Institutes of Health (NIH) discretionary grant opportunity (Funding Opportunity Number RFA AI 16 081) designed to speed up antibiotic and antibacterial therapeutic discovery by improving the early-stage tools used to evaluate whether small molecules can actually work in hard-to-treat Gram-negative bacteria. The focus is not simply on finding new drug candidates, but on building and applying practical, predictive research tools that make discovery more efficient and more likely to translate into real treatments.

The core scientific problem this FOA targets is one of the biggest barriers in Gram-negative antibacterial development: many compounds that look promising in standard laboratory screens fail because they cannot get to their bacterial targets at effective concentrations. Gram-negative pathogens have an additional outer membrane barrier and often possess strong efflux systems that actively pump small molecules back out of the cell. This FOA therefore emphasizes projects that develop and use novel predictive assays, models, and other research tools centered specifically on two linked determinants of antibacterial success: penetration (how well a compound enters and accumulates inside the bacterium) and efflux (how strongly the bacterium removes the compound). The intent is to generate tools that help researchers predict which chemical matter is most likely to be viable as a therapeutic, earlier in the pipeline, and to guide medicinal chemistry and optimization efforts more rationally.

The announcement is scoped to therapeutic discovery efforts aimed at select high-priority antimicrobial-resistant Gram-negative pathogens, specifically carbapenem-resistant Enterobacteriaceae (CRE), multidrug-resistant (MDR) Acinetobacter, and/or MDR Pseudomonas aeruginosa. These organisms are major public health threats because they cause severe infections and can be resistant to many or most available antibiotics, including last-line drugs. By concentrating on these pathogens, the FOA is aligned with urgent clinical need and with broader national and global efforts to address antimicrobial resistance.

A defining feature of the program is that it supports milestone-driven projects. In practice, that means applicants are expected to propose a clear development plan with measurable go/no-go checkpoints, demonstrating how the proposed assays or models will be built, validated, and then used in a way that meaningfully advances therapeutic discovery against the targeted bacteria. The emphasis on milestones signals that funders want tool development that is not purely exploratory, but engineered toward practical use, reproducibility, and decision-making value for discovery teams.

On the administrative side, this is an R01 research project grant mechanism under NIH, with Health-related Funding Activity Category and CFDA numbers 93.855 and 93.856. The listed award ceiling is $1,050,000. The opportunity was created on 2016-11-16 and the original closing date was 2017-05-17, which places it in a specific historical funding cycle, though the summary goals remain a useful indicator of NIH priorities in antibacterial tool development.

Eligibility is broad and includes many types of U.S. and non-U.S. organizations. Eligible applicants span state, county, and local governments; special districts; independent school districts; public and state-controlled institutions of higher education; private institutions of higher education; Native American tribal governments (federally recognized); Native American tribal organizations (other than federally recognized tribal governments); public housing authorities/Indian housing authorities; nonprofits with and without 501(c)(3) status (excluding institutions of higher education in those categories); for-profit organizations other than small businesses; and small businesses. The FOA also explicitly highlights additional eligible applicant categories, including Alaska Native and Native Hawaiian Serving Institutions; Asian American Native American Pacific Islander Serving Institutions (AANAPISI); Hispanic-serving Institutions; Historically Black Colleges and Universities (HBCUs); Tribally Controlled Colleges and Universities (TCCUs); eligible federal agencies; faith-based or community-based organizations; regional organizations; U.S. territories or possessions; Indian/Native American tribal governments other than federally recognized; and non-domestic (non-U.S.) entities (foreign organizations). This breadth supports cross-sector partnerships, including academic, nonprofit, government, and industry participants, which is often necessary to build robust discovery-enabling tools and to test them in realistic drug development contexts.

Overall, the opportunity is best understood as a targeted investment in the enabling science of Gram-negative antibiotic discovery: creating and validating better predictive assays and models of compound penetration and efflux so that researchers can more quickly identify, optimize, and advance potential therapeutics for CRE, MDR Acinetobacter, and MDR Pseudomonas aeruginosa, where traditional screening and optimization approaches frequently fail.

• The National Institutes of Health in the health sector is offering a public funding opportunity titled "Partnerships for the Development of Tools to Advance Therapeutic Discovery for Select Antimicrobial-Resistant Gram-Negative Bacteria (R01)" and is now available to receive applicants.
• Interested and eligible applicants and submit their applications by referencing the CFDA number(s): 93.855, 93.856.
• This funding opportunity was created on 2016-11-16.
• Applicants must submit their applications by 2017-05-17. (Agency may still review applications by suitable applicants for the remaining/unused allocated funding in 2026.)
• Each selected applicant is eligible to receive up to $1,050,000.00 in funding.
• Eligible applicants include: State governments, County governments, City or township governments, Special district governments, Independent school districts, Public and State controlled institutions of higher education, Native American tribal governments (Federally recognized), Public housing authorities/Indian housing authorities, Native American tribal organizations (other than Federally recognized tribal governments), Nonprofits having a 501 (c) (3) status with the IRS, other than institutions of higher education, Nonprofits that do not have a 501 (c) (3) status with the IRS, other than institutions of higher education, Private institutions of higher education, For-profit organizations other than small businesses, Small businesses, Others.

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