A Novel Screen for Antibacterials that Are Non-Toxic to Mammals

一种对哺乳动物无毒的抗菌药物的新型筛选

基本信息

批准号：
9015218
负责人：
Corrella S Detweiler
金额：
$ 18.64万
依托单位：
UNIVERSITY OF COLORADO
依托单位国家：
美国
项目类别：
财政年份：
2015
资助国家：
美国
起止时间：
2015-12-01 至 2017-11-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9015218
关键词：
Anti-Bacterial Agents Antibiotics Antimicrobial Resistance Bacteria Biochemical Biological Assay Cell membrane Cells Chemosensitization Collection Disease Diversity Library Dose Drug Kinetics Face Goals Gram-Negative Bacteria Growth Housing Human Lead Mammalian Cell Mammals Manufacturer Name Membrane Potentials Modeling Molecular Target Monitor Morbidity - disease rate Multi-Drug Resistance Mus Pharmaceutical Preparations Phase Phylogenetic Analysis Preparation Property Protocols documentation Resistance Salmonella Structure-Activity Relationship System Systemic infection Testing Toxic effect Trees Virulence Virulence Factors Virulent analog bacterial genetics base cell type cytokine cytotoxicity in vivo indexing macrophage mitochondrial membrane mortality novel novel therapeutics pathogen prevent public health relevance quantitative imaging response scaffold screening small molecule therapeutic target

项目摘要

DESCRIPTION (provided by applicant): There is a critical need for novel therapeutics to treat antimicrobial-resistant Gram-negative bacteria. Historically, antibiotics were identified in screen using whole bacteria. Over the past 20 years, there has instead been intensive biochemical screening that targets bacterial molecules, an approach that has often identified compounds with significant barriers in either the pathogen or the mammalian host, including an inability to enter or remain within host or pathogen cells, destruction by the host or pathogen, or host cytotoxicity. We have therefore developed a quantitative, image-based high content screen that excludes compounds with undesirable properties because it uses whole, virulent, bacteria growing within mammalian cells. We propose to use this screen to identify therapeutics that target nonessential bacterial virulence factors and will be effective against antimicrobial-resistant bacteria.

描述（由适用提供）：新的治疗需要进行抗菌革兰氏阴性细菌。从历史上看，使用全细菌在筛选中鉴定出抗生素。在过去的20年中，靶向细菌分子的强化生化筛选，这种方法通常鉴定出病原体或哺乳动物宿主具有明显障碍的化合物，包括无法进入或留在宿主或病原细胞内，宿主或病原体或宿主的细胞毒性。因此，我们开发了一个基于图像的高内容屏幕，该屏幕排除具有不良特性的化合物，因为它使用了哺乳动物细胞中生长的整个，有毒的细菌。我们建议使用此筛选来鉴定靶向非必要细菌病毒因子的疗法，并有效地抗菌抗菌细菌。