Discovering Antimicrobial Drugs from Symbiotic Actinobacteria from Terrestrial

从陆地共生放线菌中发现抗菌药物

• 批准号: 9235229
• 负责人: Cameron Robert Currie
• 金额: $ 55.19万
• 依托单位: UNIVERSITY OF WISCONSIN-MADISON
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/9235229
• 关键词: Acquired Immunodeficiency Syndrome; Actinobacteria class; Anti-Bacterial Agents; Antibiotic Resistance; Antibiotics; Antifungal Agents; Bacteria; Bioinformatics; Biological; Biological Assay; Cells; Cessation of life; Chemicals; Coculture Techniques; Collaborations; Collection; Communicable Diseases; Communities; Development; Drug resistance; Environment; Evolution; Genome; Genomic approach; Goals; Health; Human; In Vitro; Individual; Insecta; Lead; Link; Methicillin Resistance; Methods; Microbe; Mycoses; Natural Products; Parasites; Pathogenicity; Perception; Pharmaceutical Preparations; Pharmacologic Substance; Prodrugs; Production; Public Health; Research; Resistance; Sampling; Soil; Source; Staphylococcus aureus; Streptomyces; System; Technology; Testing; Therapeutic; Translations; Tuberculosis; United States; Work; antimicrobial; antimicrobial drug; base; cytotoxicity; drug discovery; drug mechanism; fungus; improved; metabolome; metabolomics; multidisciplinary; next generation sequencing; novel; novel therapeutics; pathogen; small molecule; success; tool

Natural products serve as critical drugs or drug precursors with broad pharmaceutical application, including serving as the most effective antibiotics. The widespread and rapid evolution of antibiotic-resistance in pathogenic microbes makes the discovery of novel therapeutics to treat infectious diseases of urgent importance. Despite this critical need, small molecule discovery has decreased substantially in recent decades and the pipeline of new antibiotics is rapidly diminishing. The broad goals of this project are to discover novel antibiotics with high therapeutic potential by identify new natural products from insect associated Actinobacteria (aim 1), using next-generation sequencing technology and bioinformatics to help discover novel compounds from symbiotic microbes (aim 2), and evaluating the natural products discovered in SAI and SA2 for their therapeutic potential (aim 3). Through its direct integration with the multidisciplinary team in the center, the work proposed holds the promise to generate numerous new drug leads with therapeutic potential, result in a new paradigm in drug discovery, and, by translation, to impact the treatment of drug-resistant infectious diseases on a global scale.

天然产物是关键药物或药物前体，具有广泛的制药应用，包括作为最有效的抗生素。病原微生物的耐药性的广泛和快速演变使得发现治疗感染性疾病的新疗法具有迫切的重要性。尽管有这种迫切的需求，但近几十年来小分子的发现大幅减少，新抗生素的管道正在迅速减少。该项目的广泛目标是通过从昆虫相关放线菌中鉴定新的天然产物来发现具有高治疗潜力的新型抗生素（目标1），使用下一代测序技术和生物信息学来帮助从共生微生物中发现新化合物（目标2），并评估SAI和SA2中发现的天然产物的治疗潜力（目标3）。通过与中心多学科团队的直接整合，这项工作有望产生许多具有治疗潜力的新药，导致药物发现的新范式，并通过转化影响全球范围内耐药传染病的治疗。