EAGER: Developing Biological drones for attacking targeted bacteria

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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.