Introduction The National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), of the Department of Health and Human Services (DHHS) supports research related to ... Introduction The National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), of the Department of Health and Human Services (DHHS) supports research related to the basic understanding of microbiology and immunology leading to the development of vaccines, therapeutics, and medical diagnostics for the prevention, treatment, and diagnosis of infectious and immune-mediated diseases. The NIAID, Division of Microbiology and Infectious Diseases (DMID) has a requirement for creating a new Chemistry Center for Combating Antibiotic-Resistant Bacteria (CC4CARB) responsible for coordinating and conducting the design, synthesis and delivery of chemical libraries of novel small-molecules and discrete natural products with diverse physicochemical properties, specifically designed to target Gram-negative bacterial pathogens. Background Multidrug-resistant (MDR) bacteria are key pathogens responsible for the alarming rates of drug resistance in healthcare and community settings. The Centers for Disease Control and Prevention (CDC) has developed a list of organisms considered Antimicrobial Resistance (AMR) threats. Many of these organisms are MDR Gram-negative bacteria, including carbapenem-resistant Enterobacteriaceae, MDR Acinetobacter, and MDR Pseudomonas aeruginosa. Resistance has evolved over the past decade to the point that for some infections there are no effective treatment options. The problem is exacerbated by the scarcity of novel compounds effective against the modern cohort of drug-resistant bacteria and the current antibacterial drug discovery pipeline is inadequate to the need. In publications and public forums (such as NIAID workshops), the antibacterial research community has identified the lack of suitable compound screening libraries and novel chemical scaffolds as a significant bottleneck for the discovery and development of novel antibacterial drugs. In particular, there is a scarcity of novel chemical classes and natural compounds with properties appropriate for Gram-negative cell penetration (and efflux avoidance). Most public and privately held compound libraries are enriched with compounds previously designed for human targets and pathways and, thus, they are poorly suited as starting points for discovery of drugs that should avoid human targets and pathways, and which require properties for bacterial cell penetration rather than mammalian cell penetration. In a report produced with the help of key opinion leaders by the PEW Charitable Trust titled “Scientific Roadmap for Antibiotic Discovery,” the lack of appropriate chemical libraries is recognized as one of the key problems in antibacterial drug discovery. This report states that the need to “generate and tailor chemical matter for antibacterial discovery” and to “build prototype libraries tailored for antibacterial discovery” is a fundamental part of the critical path to new antibacterial agents. Only recently have rules emerged that describe chemical space for improved antibacterial activity, though these are still neither comprehensive nor fully understood. We expect continued focused academic and industrial research to expand and refine this nascent understanding and we anticipate CC4CARB will leverage it in the design, synthesis, and in vitro testing of new antibacterial compounds. The aim of this solicitation is to continue the Chemistry Center for Combating Antibiotic-Resistant Bacteria (CC4CARB) responsible for coordinating and conducting the design, synthesis, in vitro testing, and distribution of chemical libraries of discrete natural products and small-molecules with diverse physicochemical properties, specifically designed to target Gram-negative bacterial pathogens and other antibiotic-resistant bacteria identified as Antimicrobial Resistance threats. The contract shall consist of requirements in four (4) key areas: 1) Library Design, 2) Compound Synthesis, 3) Compound Testing, and 4) Compound Management, and includes Project Management of all efforts across these requirements. It is anticipated that one (1) cost-reimbursement, level-of-effort type contract will be awarded with a one-year base period beginning on or around February 1, 2026. The award is anticipated to include four (4) one-year term option periods. In addition, there will be three (3) one (1) year term options for compound management and distribution support that may only be exercised after Term Options A1-A4 have been exhausted. There are four (4) quantity options per performance year that may be exercised at any time within their respective performance years for the first five (5) years of contract performance. The total period of performance, if all term and quantity options are exercised, shall be on/around February 2034. The Government’s level-of-effort requirement is estimated at 28,000 direct labor hours for the base year and each term option (A1-A4). The Government’s level-of-effort requirement for each quantity option is estimated at 2,000 direct labor hours. The Government’s level-of-effort requirement is estimated at 4,000 direct labor hours for each term option A5-A7. The Government anticipates producing 10,000 rationally designed and structurally diverse compounds over the period of the contract. Any responsible offeror may submit a proposal which will be considered by the Agency. This RFP will be available electronically on/about November 30, 2024, and may be accessed through https://sam.gov/. This notice does not commit the Government to award a contract. No collect calls will be accepted. No facsimile transmissions will be accepted. For this solicitation, the NIAID requires proposals to be submitted online via the NIAID electronic Contract Proposal Submission (eCPS) website. Submission of proposals by facsimile or e-mail is not acceptable. For directions on using eCPS, go to the website https://ecps.nih.gov/ and then click on "How to Submit."