Identification of novel natural products active against MDR pathogens

鉴定具有抗 MDR 病原体活性的新型天然产物

• 批准号: 8832671
• 负责人: Marc Sharp
• 金额: $ 19.94万
• 依托单位: LINNAEUS BIOSCIENCE, INC.
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-08-01 至 2017-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8832671
• 关键词: Actinobacteria class; Anti-Bacterial Agents; Antibiotic Therapy; Antibiotics; Antifungal Agents; Bioinformatics; Biological Factors; Businesses; Cells; Collaborations; Collection; Communities; Crude Extracts; Drug Industry; Fee-for-Service Plans; Fluorescence Microscopy; Future; Gene Cluster; Genes; Genome; Goals; Hour; Individual; Lead; Mass Spectrum Analysis; Measures; Methods; Mining; Pathway interactions; Property; Source; Streptomyces; Techniques; Technology; Work; base; drug resistant bacteria; experience; genome sequencing; interest; multi-drug resistant pathogen; novel; novel strategies; overexpression; pathogen; programs; public health relevance; screening; tumor

 DESCRIPTION (provided by applicant): The need for new antibiotics that are active against multidrug resistant pathogens has created renewed interest in discovering antibiotics from sources of natural products. We have developed a new approach, bacterial cytological profiling (BCP), that uses quantitative fluorescence microscopy to measure the effects of antibiotic treatment on individual cells. Antibiotics that target different cellular pathways and different steps within a pathway generate unique cytological profiles, allowing identification of the likely MOA of new compounds within a few hours. BCP is especially useful for identification of natural products in crude natural product extracts because it rapidly discriminates between antibiotics with different mechanisms of action (MOA). The BCP screening platform can detect nuisance compounds and multiple activities in partially purified or crude natural product extracts and it can detect active molecules at sub-inhibitory concentrations. The goal of this project is to develop a comprehensive natural product identification platform that combines BCP with genome mining methods to rapidly identify novel molecules and their biosynthetic gene clusters. Linnaeus Bioscience Inc. is a start up company founded to commercialize this technology and make it accessible on a fee for service basis to the pharmaceutical industry and the scientific community. This proposals describes a set of specific aims that will allow us to develop a simple, robust platform for discovering novel natural products active against drug resistant bacteria.

 描述（由申请人提供）：对新抗生素的需求，对多药耐药病原体的活性，创造了新的兴趣，发现抗生素的天然产品来源。我们已经开发了一种新的方法，细菌细胞学分析（BCP），使用定量荧光显微镜来测量抗生素治疗对单个细胞的影响。靶向不同细胞途径和途径内不同步骤的抗生素产生独特的细胞学特征，允许在几小时内鉴定新化合物的可能MOA。BCP对于天然产物粗提物中天然产物的鉴定特别有用，因为它可以快速区分具有不同作用机制（MOA）的抗生素。BCP筛选平台可以检测部分纯化或粗天然产物提取物中的有害化合物和多种活性，并且可以检测亚抑制浓度的活性分子。该项目的目标是开发一个综合的天然产物鉴定平台，将BCP与基因组挖掘方法相结合，以快速鉴定新分子及其生物合成基因簇。Linnaeus Bioscience Inc是一家初创公司，旨在将这项技术商业化，并使其在服务收费的基础上向制药行业和科学界开放。该提案描述了一系列具体目标，使我们能够开发一个简单，强大的平台，用于发现对耐药细菌具有活性的新型天然产物。