Identification of novel MDR antimicrobials from insect-Streptomyces symbioses

从昆虫-链霉菌共生体中鉴定新型耐多药抗菌剂

• 批准号: 10592386
• 负责人: Cameron Robert Currie
• 金额: $ 129.57万
• 依托单位: UNIVERSITY OF WISCONSIN-MADISON
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-04-01 至 2025-03-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10592386
• 关键词: Identification; novel; MDR; antimicrobials; insect

Abstract To combat the constant emergence of multidrug-resistant pathogens, the discovery of structurally novel natural products with antimicrobial properties is a critical need. As part of the Wisconsin Antimicrobial Drug Discovery and Development Center, we will address the urgent need for new antimicrobial drug leads by exploiting an innovative source: Streptomyces symbionts of insects. In our preliminary work we have shown that these Actinobacteria represent a rich and largely untapped source of novel antimicrobials with therapeutic potential. For example, we have shown in vivo (murine) safety and efficacy against Gram-negative bacterial and fungal human pathogens for several dozen lead molecules. In addition, we have confirmed antifungal efficacy and safety in our FDA-enabling murine model for our drug lead Cyphomycin, a novel molecule we discovered from an insect-Streptomyces. In our approach, we will also apply new genomic and metabolomic approaches, along with ecologically-informed bioassays. Our research will help reinvigorate the antimicrobial discovery pipeline and identify new MDR active drug leads.

摘要 为了对抗不断出现的多药耐药病原体，发现结构新颖的天然 具有抗微生物性能的产品是一个关键的需求。作为威斯康星州抗菌药物发现计划的一部分， 和开发中心，我们将通过开发新的抗微生物药物先导物来满足迫切需要， 创新来源：昆虫共生链霉菌。在我们的初步工作中，我们已经表明， 放线菌代表了具有治疗潜力的新型抗微生物剂的丰富且大部分未开发的来源。 例如，我们已经显示了在体内（鼠）对革兰氏阴性细菌和真菌的安全性和有效性， 人类病原体中几十种铅分子。此外，我们已经证实了抗真菌的疗效， 安全性在我们的FDA使我们的药物先导Cyphomycin小鼠模型，一种新的分子，我们发现从 一种昆虫链霉菌在我们的方法中，我们还将应用新的基因组学和代谢组学方法，沿着 生态学上的生物测定我们的研究将有助于重振抗菌剂发现管道， 确定新MDR活性药物先导化合物。