Project Summary: OverallResistance to antimicrobial therapies is a national and international crisis that threatens clinical practice fromfundamental primary care to the most advanced medical interventions such as cancer chemotherapy andorgan transplantation. Much of what we take for granted in clinical medicine could become too risky asmicroorganisms have become increasingly resistant to our newest medications and our antibiotics of lastresort. Antimicrobial resistance also adds enormous costs to health care, exceeding $21 billion in the UnitedStates alone. Compounding this problem is the fact that pharmaceutical companies have largely abandonedantibiotic development programs. As an alternative to large pharmaceutical companies, academic institutionsand biotech startups can step in to refill the antibiotic pipeline using novel approaches to drug discovery. Theprincipal objective of this Phase I COBRE application is to build a unique, multi-disciplinary center ofexcellence to study mechanisms of antimicrobial resistance and develop therapeutic countermeasures. Thelong-term goal of the Center for Antimicrobial Resistance and Therapeutic Discovery (CARTD) at The MiriamHospital of the Lifespan Hospital Group is to develop new therapies for infections caused by drug resistantpathogens. This long-term goal will be attained with shorter-term objectives of developing a new generation ofjunior investigators who study mechanisms of resistance, characterize new targets, and study new and existingcompounds. CARTD will integrate their work with mentors and established investigators at the institution anddevelop core facilities to enhance research capabilities in the field of antimicrobial resistance and the discoveryof new therapeutics. To achieve these objectives, the CARTD will complete the following specific aims: 1.Consolidate existing researchers into a dynamic, interactive center of excellence across The Miriam Hospital,and its academic partners in Rhode Island, including Brown University. 2. Foster the research programs andcareer development of junior investigators in the field of antimicrobial resistance and studies of noveltherapeutic approaches. 3. Support new institutional research with pilot project funding. 4. Establish criticalinfrastructure with new core laboratories to facilitate cutting edge research in antimicrobial resistance andtherapeutic discovery, and serve as a unique technical resources to other COBRE research programs, otherinstitutional researchers, and investigators in the region.