Core D In vitro Screening

摘要 微生物体外筛选（IVS）核心将提供全面的药敏试验 包括五个项目的候选化合物的一系列测定。的项目 代表不同的发展阶段，需要个别考虑。但 所有5个项目的共同点是要求进行全细胞筛选。的资源 IVS核心的专业知识包括巨噬细胞感染模型和细胞内易感性， 浓度依赖性杀伤与时间依赖性杀伤，小菌落变体，抗生物膜 效力、血清转移实验、稳定期或“百日龄”培养物、耐药 突变体的产生和分析以及药物组合分析。药物反应与 评估突变体的形成/预防和其他先进的分析也可用。化合物 将结合药物化学核心（核心B）确认纯度。数据 将使用Collaborative Drug Discovery，Inc. 软件程序（参见数据共享）。筛选核心收集的生物体包括 28种病原体康奈尔博士和巴里·克莱斯博士的实验室 （PHRI）提供了广泛的临床菌株集合，其充分表征了抗生素抗性， 与纽约/新泽西的私立、公立和退伍军人管理局医院合作， 大都市地区以及世界各地的医院将在本世纪后期提供服务 项目，以确定阻力概况。BSL 2、BSL 3和特选药剂BSL 3实验室 为安全使用这种广泛的菌株收集提供了条件。该小组聚集在一起， 这些体外测定在细菌药物发现方面具有超过65年的综合经验， 抗生素敏感性和耐药性分析。该集团的中等吞吐量经验 高精度和快速周转是一个重要的和必要的贡献， 项目的成功。 !

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. !