Discovery of Novel Antibiotic Natural Products from Marine-Derived Fungi

项目摘要/摘要 人类健康未来面临的一大挑战是抗药性病原菌的崛起。2017年 世界卫生组织(WHO)公布了一份12种病原体的名单，这些病原体将对 由于对一线治疗的抗药性而导致的人类健康。这个项目的总体目标将是确定新的 对世卫组织病原体表现出抗生素活性的真菌天然产品。天然产品是 生物体产生的次生代谢物。这些小分子化学物质起到了 几千年来在传统医学中扮演着重要的角色，是当前治疗方法的重要组成部分 阿森纳的现代医学。该项目将通过两个方面的研究来实现总体目标。第一 该领域涉及开发一种快速去复制方法，以减少培养中多余的真菌菌株 图书馆，以简化生物筛选。第二个问题是确定抗生素药物的先导 新型化学支架或通过独特的抗世卫组织毒力作用机制发挥作用的化学支架 病原体。一旦完成，这两个领域的研究将连接起来，开发一种真菌代谢物药物 发现平台，将用于促进未来的生物医学研究。

Project Summary/Abstract A major challenge facing the future of human health is the rise of antibiotic-resistant pathogenic bacteria. In 2017 the World Health Organization (WHO) published a list of twelve pathogens that will pose the greatest threat to human health due to resistance to frontline treatments. The overall goal of this project will be to identify novel fungal natural products that exhibit antibiotic activity towards the WHO pathogens. Natural products are secondary metabolites produced by living organisms. These small molecule chemical entities have played an important role in traditional medicine for thousands of years and are an essential part of the current therapeutic arsenal for modern medicine. This project will achieve the overall goal through two areas of research. The first area involves the development of a rapid dereplication method that reduces redundant fungal strains in culture libraries to streamline biological screening. The second involves the identification of antibiotic drug-leads with novel chemical scaffolds or that function through a unique antivirulence mechanism of action against the WHO pathogens. Once completed, these two areas of research will be bridged to develop a fungal metabolite drug discovery platform that will be used to promote future lines of biomedical research.