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.

抽象的 为了应对多种耐药病原体的不断出现，发现结构新颖的自然 具有抗菌特性的产品是迫切需要的。作为威斯康星州抗菌药物发现的一部分 和开发中心，我们将通过利用一个 创新来源：昆虫的链霉菌共生。在我们的初步工作中，我们证明了这些 放线菌是具有治疗潜力的丰富且在很大程度上未开发的新型抗菌剂来源。 例如，我们显示了针对革兰氏阴性细菌和真菌的体内（鼠）安全性和功效 人类病原体几十个铅分子。此外，我们已经确认了抗真菌功效和 在我们的药物铅Cyphomycin的FDA增强鼠模型中的安全性，我们从中发现了一种新的分子 昆虫诱变。在我们的方法中，我们还将采用新的基因组和代谢组方法 具有生态信息的生物测定。我们的研究将有助于振兴抗菌发现管道和 识别新的MDR活性药物铅。