Core D In vitro Screening

核心D体外筛选

• 批准号: 10613890
• 负责人: BARRY Neal KREISWIRTH
• 金额: $ 53.99万
• 依托单位: HACKENSACK UNIVERSITY MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-05-01 至 2024-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10613890
• 关键词: Acinetobacter baumannii; African Green Monkey; Anti-Bacterial Agents; Antibiotic Resistance; Antibiotic susceptibility; Area; Bacillus anthracis; Bacillus cereus; Bacteria; Biological Assay; Burkholderia cepacia; Cell Line; Cells; Clinical; Collaborations; Collection; Computer software; Data; Development; Drug Combinations; Drug resistance; ESKAPE pathogens; Enterobacter; Enterococcus faecium; Epithelium; Francisella tularensis; Frequencies; Generations; Hospitals; In Vitro; Individual; Infection; Inhibition of Cell Proliferation; Kidney; Klebsiella pneumoniae; Laboratories; Macrophage; Mammalian Cell; Metabolic; Methodology; Microbial Biofilms; Minimum Inhibitory Concentration measurement; Modeling; Molecular; Multi-Drug Resistance; Mus; Mycobacterium abscessus; Mycobacterium fortuitum; Mycobacterium marinum; Mycobacterium smegmatis; Mycobacterium tuberculosis; Neisseria gonorrhoeae; New Jersey; New York; Organism; Pathogenicity; Pharmaceutical Chemistry; Pharmaceutical Preparations; Phase; Phenotype; Predisposition; Prevention; Privatization; Pseudomonas aeruginosa; Resistance; Resistance profile; Resources; Serum; Staphylococcus aureus; Statistical Data Interpretation; System; Testing; Therapeutic; Time; Variant; Yersinia pestis; bacterial resistance; candidate selection; cytotoxicity; data sharing; drug discovery; experience; experimental study; in vitro Assay; innovation; metropolitan; microbial; mutant; mycobacterial; pathogen; programs; resistance mechanism; response; screening; success

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. !

抽象的 微生物体外筛查（IVS）核心将提供全面的敏感性测试 涵盖了五个项目的候选化合物的一系列测定法。项目 代表开发的各个阶段，需要个人考虑。但是， 通过所有5个项目的共同线程是全细胞筛选的要求。资源 IVS核心的专业知识包括巨噬细胞感染模型和细胞内敏感性， 浓度依赖性杀戮与时间依赖性杀戮，小菌落变体，抗双膜 功效，血清移位实验，固定相或“一百年历史”培养物，耐药性 突变产生和分析以及药物组合分析。药物反应关系 还提供评估突变体形成/预防和其他高级分析。化合物 纯度将被确认与药物化学核心（核心B）结合使用。数据 合规性和存储将使用协作药物发现公司进行处理和共享。 软件程序（请参阅数据共享）。放映核心收藏中的生物包括 28种病原体。 Connell博士和Barry Kreiswirth博士的实验室 （PHRI）提供了广泛的临床菌株集合，具有抗生素耐药性的特征， 与纽约/新泽西州的私立，公立和VA医院合作组装 大都市地区以及世界各地的医院将在 定义电阻概况的项目。 BSL2，BSL3和Select Agent BSL3实验室是 旨在安全地使用此广泛的应变收集。团队集会进行 这些体外测定的综合经验超过65年。 分析抗生素敏感性和抗性。小组的中等吞吐量经验 高精度和快速周转是对整体的重要贡献 项目的成功。 呢