Protecting microbes so they can protect us

项目摘要 尽管有压倒性的证据表明微生物对维持人类健康的重要性， 由于大多数药物目前无法生产，因此开发治疗药物受到阻碍。很长的- 这项工作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 从加工、运输和储存的压力。所提出的涂层已被证明可以保护 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，包括 冷冻干燥，紫外线照射，极端温度和高湿度？本申请的总体目标是 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， 将建立具有不同组成的涂层的物理和化学性质。这些能力 保护治疗相关微生物菌株免受加工、储存和运输应力的涂层 将被研究。最后，通过结合暴露于压力源后微生物存活的发现， 纳米涂层的物理化学表征，将开发一种算法来预测最佳的 用于任何感兴趣的新菌株的涂层，而不需要筛选以鉴定具有 所需的保护性能。这项工作将提供基本的见解，这些物理特性 纳米涂层和这些性能对微生物生存力的影响。这些知识将使 生产重要但具有挑战性的微生物治疗剂，前所未有的轻松。即使是部分成功 这项工作将产生前所未有的信息，如何最好地保护微生物在生产过程中， 阐明保护机制。这些知识可以直接促进和改善 治疗学微生物药物作为治疗难以治疗的疾病特别有吸引力， 耐多药感染和耐化疗的癌症，在其发展方面取得任何进展 非常重要这项技术不仅能够开发新的治疗方法， 通过在非理想环境中交付和储存这些生物制剂，使全球能够公平获得这些生物制剂。

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.