Core E Animal Infection Models

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Abstract Assessing the treatment efficacy of novel leads against drug resistant bacteria in animal models is crucial for advancing compounds to the preclinical stage of development. Currently, there is a paucity of reproducible disease models with reliable metrics to assess lead compounds and even less facilities and personnel with the expertise to perform such important studies. To meet this important challenge, the Animal Model Core for this proposed CETR has developed reproducible systemic, pulmonary, soft tissue, wound, infection models in rodents for clinically important multidrug resistant bacteria. The Aims of the core are to: 1) provide small animal infection models for ESKAPE, TB and NTM pathogens to evaluate lead compounds, and 2) provide state of the art analytical services on host response and bacterial bio-burden distribution to assess and quantify lead compound treatment efficacy. The Animal core has functioned in this capacity for more than 15 years with experience supporting drug development for the academic, pharma and biotech sectors. Under the direction of Dr. David Perlin, it served as a multi-institutional regional animal core for the Region II RCE (Northeast Biodefense Center) for 11 years (2003-2013) and has supported the current CETR for the past 4+ years (2013 to present). The Animal Core operates at a very high capacity, having logged more than 1.8 million animal days of high threat bacterial agents since 2003. An experienced and dedicated animal model team performs a wide range of infection models with multiple routes of infections (iv, oral, aerosol, subcutaneous, mucosal) and markers for disease (morbidity/mortality, microbial burden, histopathology, etc.). The management staff of the Animal core works closely with both Project Leaders and other Core Directors to ensure that all novel leads are rapidly advanced through the development pipeline. This close and constant line of communication permits the necessary adjustments in design and execution of studies, and has resulted in the advancement of 7 promising leads in the Rutgers CETR projects from 2014 to 2018. the Animal core possesses cutting edge instrumentation for analysis of infections and therapeutic responses. The incorporation of reproducible animal models operated by highly experienced staff and utilizing novel technologies will advance and accelerate the development of promising Lead compounds against multidrug resistant bacteria. All services can be performed under high-level biocontainment with regulatory approval. !