Protecting microbes so they can protect us

保护微生物，让它们可以保护我们

• 批准号: 10687576
• 负责人: Ariel Lesa Furst
• 金额: $ 143.1万
• 依托单位: MASSACHUSETTS INSTITUTE OF TECHNOLOGY
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-09-18 至 2026-08-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10687576
• 关键词: Algorithms; Antibiotic Therapy; Biological Products; Chemoresistance; Development; Disease; Environment; Equity; Exposure to; Freeze Drying; Goals; Health; Human; Humidity; Infection; Knowledge; Malignant Neoplasms; Medicine; Microbe; Multi-Drug Resistance; Patient-Focused Outcomes; Production; Property; Public Health; Quality of life; Stress; Technology; Therapeutic; Transportation; Ultraviolet Rays; Work; antibiotic resistant infections; beneficial microorganism; chemical property; environmental stressor; extreme temperature; improved; insight; interest; manufacture; microbial; nanomaterials; nanoscale; novel; novel therapeutics; physical property; refractory cancer; screening; self assembly; stressor; success; therapeutic development

PROJECT SUMMARY Despite overwhelming evidence demonstrating the importance of microbes to maintain human health, efforts to develop them as therapeutics are impeded because most are currently impossible to manufacture. The long- term goal of this work is to develop self-assembling nanomaterials as a universal “shield” to protect any microbe from processing, transportation, and storage stresses. The proposed coatings have been shown to protect both Gram-positive and Gram-negative strains during freeze-drying and subsequent storage in non-ideal conditions. These results beg the question: how do the coatings protect microbes from environmental stressors, including freeze-drying, UV-light exposure, extreme temperatures, and high humidity? The overall aim of this application is to elucidate the mechanism of microbial protection afforded by these coatings. To accomplish this goal, the physical and chemical properties of coatings with diverse compositions will be established. The ability of these coatings to protect therapeutically-relevant microbial strains from processing, storage, and transport stresses will then be studied. Finally, by combining findings on microbial survival upon exposure to stressors with physicochemical characterization of the nanoscale coatings, an algorithm will be developed to predict optimal coatings for any novel strain of interest without necessitating screening to identify coating compositions with the desired protective properties. This work will provide fundamental insights into the physical properties of these nanoscale coatings and the impact of these properties on microbial viability. This knowledge will enable the production of important but challenging microbial therapeutics with unprecedented ease. Even partial success in this work will yield unprecedented information on how best to protect microbes during manufacture by elucidating the mechanism of protection. This knowledge can directly enable and improve the development of therapeutics. Microbial medicines are especially attractive as treatments for hard-to-treat diseases such as multidrug-resistant infections and chemotherapy-resistant cancers, making any progress in their development highly important. Not only will this technology enable the development of new therapeutics, it will also provide equitable global access to such biologics by enabling their delivery and storage in non-ideal environments.

项目概要 尽管大量证据表明微生物对维持人类健康的重要性，但努力 由于大多数目前无法制造，因此治疗方法的开发受到阻碍。长- 这项工作的长期目标是开发自组装纳米材料作为保护任何微生物的通用“盾牌” 免受加工、运输和储存压力。所提出的涂层已被证明可以保护两者 冷冻干燥和随后在非理想条件下储存期间的革兰氏阳性和革兰氏阴性菌株。 这些结果引出了一个问题：涂层如何保护微生物免受环境压力源的影响，包括 冷冻干燥、紫外线照射、极端温度和高湿度？本申请的总体目标 目的是阐明这些涂层提供的微生物保护机制。为了实现这一目标， 将确定具有不同成分的涂层的物理和化学特性。这些能力 保护与治疗相关的微生物菌株免受加工、储存和运输压力的涂层 然后将被研究。最后，通过将暴露于压力源后微生物存活的发现与 纳米级涂层的物理化学特性，将开发一种算法来预测最佳 适用于任何感兴趣的新型菌株的涂层，无需筛选即可识别涂层组合物 所需的保护性能。这项工作将为这些物质的物理特性提供基本的见解 纳米级涂层以及这些特性对微生物活力的影响。这些知识将使 以前所未有的轻松生产重要但具有挑战性的微生物疗法。甚至部分成功 这项工作将产生前所未有的信息，说明如何在制造过程中最好地保护微生物 阐明保护机制。这些知识可以直接促进和改善 疗法。微生物药物作为治疗难以治疗的疾病特别有吸引力，例如 多重耐药感染和化疗耐药癌症，在其发展中取得任何进展 非常重要。这项技术不仅能够开发新疗法，还将提供 通过在非理想环境中交付和储存此类生物制品，实现全球公平获取此类生物制品。