Discovery of Novel Antibiotic Natural Products from Marine-Derived Fungi

项目总结/摘要 未来人类健康面临的一个重大挑战是耐药病原菌的兴起。2017年 世界卫生组织（WHO）发布了一份名单，列出了12种对人类构成最大威胁的病原体。 对人类健康造成的影响。该项目的总体目标是确定新的 对WHO病原体表现出抗生素活性的真菌天然产物。天然产物是 生物体产生的次级代谢物。这些小分子化学实体发挥了 数千年来，它在传统医学中发挥着重要作用，是目前治疗疾病的重要组成部分。 现代医学的武器库该项目将通过两个领域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，以减少培养物中多余的真菌菌株 文库以简化生物筛选。第二个涉及抗生素药物的鉴定， 新的化学支架或通过独特的抗WHO毒力作用机制发挥作用 病原体一旦完成，这两个研究领域将被桥接，以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.