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.

项目摘要 尽管有很多证据表明微生物对维持人类健康的重要性，但 由于目前不可能制造大多数，因此将它们发展为治疗会受到阻碍。长期 这项工作的术语目标是开发自组装纳米材料作为一种普遍的“盾牌”来保护任何微生物 从处理，运输和存储应力。提出的涂料已显示以保护两者 在非理想条件下冻干和随后的存储期间，革兰氏阳性和革兰氏阴性菌株。 这些结果引出了一个问题：涂料如何保护微生物免受环境压力源，包括 冷冻干燥，紫外线暴露，极端温度和高湿度？该应用程序的总体目的 是为了阐明这些涂层提供的微生物保护机制。为了实现这一目标， 将建立具有潜水员成分的涂料的物理和化学特性。这些能力 涂层以保护热相关的微生物菌株免受加工，存储和转运应力 然后将研究。最后，通过结合对压力源暴露于压力源的微生物存活的发现 纳米级涂层的物理表征，将开发算法以预测最佳 任何新型感兴趣的涂层，无需筛选，以鉴定与 所需的受保护特性。这项工作将提供对这些物理特性的基本见解 纳米级涂层以及这些特性对微生物生存能力的影响。这些知识将使 生产重要但挑战微生物疗法，以前所未有的轻松自然。甚至部分成功 在这项工作中，将产生有关如何最好地保护微生物在制造过程中的前所未有的信息 阐明保护机制。这些知识可以直接实现并改善 治疗。微生物药物特别有吸引力，因为治疗难以治疗的疾病，例如 多药耐药感染和抗化疗的癌症，在其发育中取得了任何进展 非常重要。这项技术不仅可以实现新疗法的开发，还将提供 公平的全球访问此类生物制剂通过使其在非理想环境中的交付和存储。