Discovering Antimicrobial Drugs from Symbiotic Actinobacteria from Terrestrial

天然产物作为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。病原微生物抗生素耐药性的广泛和快速演变使得发现治疗传染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已经大大减少，新抗生素的管道正在迅速减少。该项目的总体目标是通过鉴定昆虫相关放线菌的新天然产物（目标1），利用下一代测序技术和生物信息学帮助从共生微生物中发现新化合物（目标2），以及评估在SAI和SA2中发现的天然产物的治疗潜力（目标3）来发现具有高治疗潜力的新型抗生素。通过与该中心多学科团队的直接整合，提出的工作有望产生许多具有治疗潜力的新药，形成药物发现的新范式，并通过转化，影响全球范围内耐药传染病的治疗。

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.