Animal Model and Microbiology Core

SUMMARY Evaluating candidate compounds against drug resistant bacterial pathogens in specialized in vitro assays and robust and reproducible in vivo preclinical models predictive of human biology and disease are crucial to the advancement of compounds towards preclinical candidacy. To contribute to the rapid development of such medical countermeasures, the Animal Model and Microbiology Core will provide a collection of genetically defined drug resistant clinical isolates and clinically relevant systemic, soft tissue, pulmonary, and cardiac bacterial infection models. Specifically, the aims of the Core are to 1) provide a collection of genetically defined Gram positive, Gram negative, and NTM clinical isolates, and in vitro and ex vivo assays for advanced evaluation of lead compounds, 2) provide small animal infection models for Gram positive, Gram negative, and NTM bacterial pathogens to support evaluation of advanced lead compounds, and 3) provide state of the art analytical services on host response and bacterial bio-burden distribution to assess and quantify advanced lead compound treatment efficacy. The Core leverages the AAALAC accredited, 40,000 sq ft Center for Discovery and Innovation Research Animal Facility (CDI RAF), which has dedicated space for the study of BSL2 pathogens. Under the direction of Dr. Andrew Nelson, the CDI Research Animal Specialist Team (the Core) currently conducts model studies of mice, rats, hamsters, guinea pigs, and rabbits to support the drug development efforts of pharmaceutical and academic partners. This includes supporting concurrently a NIH supported Antiviral Drug Discovery (AViDD) Center for Pathogens of Pandemic Concern as well as a NIH Center for Excellence in Translational Research targeted at developing novel lead compounds against drug resistant bacterial infections. The experienced and dedicated animal model team routinely performs a wide range of infection models achieved through multiple routes of infection (IV, IP, aerosol, intranasal, intratracheal, intramuscular, cutaneous) and assesses these models with an array of markers for disease (microbial burden, host immune response assays, in vivo pulmonary function testing, clinical pathology, histopathology, advanced preclinical imaging modalities). Dr. Nelson is joined by Dr. Barry Kreiswirth, an expert microbiologist with extensive experience in drug resistant bacterial pathogens. The Core operations are governed by a well-developed quality control, management, and communication plan. The Core will ensure that all lead compounds are rapidly advanced through the pipeline. The Core maintains close and constant lines of communication with the Projects and other Cores to guarantee that adjustments in experimental design and throughput are executed as appropriate. Thus, the Animal Model Core is well positioned to serve the in vivo preclinical needs of the Projects in this CETR.