EAGER: Developing Biological drones for attacking targeted bacteria

生物膜是固体表面上由单个或多个细菌物种组成的细胞层。 它们会造成各种人类健康问题。例如，蛀牙是由牙齿表面上的细菌膜的活动引起的。由于它们的自我保护性质，生物膜的去除成本可能非常高，并且可能促进群体中抗生素耐药性的上升。产生耐药性的细菌可以与社区分享这种耐药性。需要新的具体方法来限制耐药性出现的时间和能力。该项目将专注于创建基于噬菌体的无人机的策略，这些无人机能够选择性地向目标细菌提供多种杀伤机制。这将有助于减少抗生素耐药性在人群中积聚的可能性。该项目还将为本科生和研究生提供噬菌体和合成生物学方面的培训，并将作出重大努力，以包括代表性不足的群体的成员。该项目的长期目标是开发一种新的策略，可以感知环境中何时存在特定的细菌，并仅在检测到该细菌时产生杀死机制。开发一种可以识别各种细菌的工程细菌混合物，根据生物膜的位置，可以以各种方式递送这些细菌，这是该项目的主要目标。这种方法可以用于在各种情况下攻击生物膜，例如在管道、货船、食品加工厂和医疗保健环境中发现的那些生物膜。该项目的近期目标是展示能够杀死金黄色葡萄球菌的噬菌体无人机的生产。具体而言，将开发用于递送细菌杀伤机制的最小噬菌体基因组并测量其功效。 这项工作将开发新的策略，以靶向破坏生物膜内的特定细菌。这项工作将提高对噬菌体生物学的理解，并将为噬菌体的使用创造新的生物技术应用。该奖项反映了NSF的法定使命，并被认为是值得通过使用基金会的智力价值和更广泛的影响审查标准进行评估的支持。

Biofilms are layers of cells on a solid surface that are composed of single or multiple bacterial species. They can create a variety of human health problems. For example, dental cavities are caused by the activity of bacterial films on tooth surfaces. As a result of their self-protective nature, biofilms can be extremely costly to remove and can promote the rise of antibiotic resistance within a population. Bacteria that become resistant can share that resistance with the community. New specific approaches that limit the time and ability for resistance to emerge are needed. This project will focus on strategies to create phage-based drones capable of selectively delivering multiple kill mechanisms to the target bacteria. This will help to reduce the potential for antibiotic resistance to build-up within the population. The project will also provide training in phage and synthetic biology for undergraduate and graduate students, with significant efforts being made to include members of underrepresented groups. The long-term goal of this project is to develop a novel strategy that can sense when a specific bacterium is present in the environment and produce the kill mechanism only when that bacterium is detected. Developing a cocktail of engineered bacteria that can recognize a variety of bacteria which could be delivered in a variety of ways depending on the location of the biofilm is a major objective of this project. This approach could be employed in attacking biofilms in a variety of contexts such as those biofilms found in pipes, on cargo ships, in food processing plants, and in healthcare settings. The immediate goal of this project is to demonstrate the production of a phage-based drone capable of killing Staphylococcus aureus. Specifically, a minimal phage genome for delivery of bacterial killing mechanisms will be developed and its efficacy measured. This work will develop new strategies to target the destruction of specific bacteria within the biofilm. This work will enhance understanding of phage biology and will create new biotechnological applications for phage use.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.