Core D In vitro Screening

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Abstract The microbial In Vitro Screening (IVS) Core will provide comprehensive susceptibility testing encompassing a range of assays for candidate compounds of the five projects. The projects represent various stages in development and require individual consideration. However, a common thread through all 5 projects is the requirement for whole cell screening. The resources and expertise of the IVS Core include macrophage infection model and intracellular susceptibility, concentration-dependent killing versus time-dependent killing, small colony variants, anti-biofilm efficacy, serum shift experiments, stationary phase or “one hundred day old” cultures, resistant mutant generation and analysis, and drug combination analysis. Drug response relationships to assess mutant formation/prevention and other advanced analysis are also available. Compound purity will be confirmed working in conjunction with the Medicinal Chemistry Core (Core B). Data conformity and storage will be handled and shared using the Collaborative Drug Discovery, Inc. software program (see Data Sharing). The organisms in the Screening Core’s collection include twenty-eight species of pathogens. The laboratories of Dr. Connell and Dr. Barry Kreiswirth (PHRI) provide extensive collections of clinical strains, well characterized for antibiotic resistance, assembled in collaboration with private, public and VA hospitals in the New York/New Jersey metropolitan area, as well as hospitals throughout the world, that will serve in later stages of the project to define resistance profiles. BSL2, BSL3 and Select Agent BSL3 laboratories are provided for the safe use of this extensive strain collection. The team assembled to carry out these in vitro assays has a combined experience of over 65 years in bacterial drug discovery and analysis of antibiotic susceptibility and resistance. The group's medium throughput experience with high precision and fast turnaround is a significant and essential contribution to the overall project’s success. !