PROJECT SUMMARY/ABSTRACT The overall objective of the Clinical Isolate Core (Core B) is to provide access to a robust collection of clinical bacterial isolates and a standardized and experimentally controlled platform for evaluating antibiotic heteroresistance (HR) for the Heteroresistance Interdisciplinary Research Unit (HR-IRU). Core B is therefore essential to the overall success of the HR-IRU program. To accomplish Core goals, we have assembled a multidisciplinary team including an infectious disease clinician (Jacob), a research scientist (Satola), a board- certified medical microbiologist (Burd) and an epidemiologist (Tunali) with expertise vast areas of antibiotic resistance. For Core B to enable successful completion of the research projects and advance our understanding of antibiotic HR we propose three specific aims. 1) To provide access to clinical bacterial isolate. Isolates (Enterobacterales and Acinetobacter baumanii complex) will be collected as part of the Centers for Disease Control and Prevention's (CDC) Georgia Emerging Infections Program (EIP) Multi-site Gram-negative Surveillance Initiative (MuGSI), Emory University's Investigational Clinical Microbiology Core (ICMC) biorepository, and Uppsala University Hospital, Sweden. 2) To profile clinical bacterial isolates for HR. We will test 500 bacterial isolates per year from bloodstream, urine, and respiratory clinical infections: 200 multi-drug resistant organisms (MDRO) from the Georgia EIP; 100 non-MDRO from the ICMC and 200 predominately susceptible isolates from Uppsala University Hospital, Sweden. Each isolate will be tested for HR to approximately 20 antibiotics using population analysis profiling (PAP), the gold standard for HR. 3) To perform epidemiological analyses revealing the prevalence, type and trends of HR. We will establish the prevalence of HR from the 2500 isolates tested in aim 2. We will perform comprehensive descriptive epidemiology on the clinical and laboratory characteristics of isolates with HR and compare those to isolates without HR. Core B will be conducted in the laboratories of the Georgia EIP and Emory University's ICMC, which have extensive expertise in active-population based surveillance and studies of HR. The Core leadership will work closely with the HR-IRU program directors/PIs and project leaders to ensure that the needs of all projects are rigorously met in a reliable, reproducible and timely manner.

PROJECT NARRATIVE In accordance with RFA-AI-20-001, the project narrative should not be completed for the scientific core.