STTR Phase I: A Platform for Systematic Acceleration of Phage-based Therapy Development for Multi-drug Resistant Bacterial Infections

The broader impact of this Small Business Technology Transfer (STTR) Phase I project is to help accelerate the opening of a second line of attack against bacterial infections that can be used in concert with or instead of traditional chemical-based antibiotics, particularly against multi-drug resistant infections. Since the discovery of penicillin, chemical-based antibiotics have been the almost exclusive choice to treat bacterial infections, but are becoming increasingly ineffective, even against infection types that were considered easily treatable twenty years ago. The traditional antibiotics global market represents almost $50 billion annually, and their use avoids trillions of dollars of potential healthcare costs, attendant suffering and loss of life. But this market is under growing threat that may reach 10 million global deaths and over one trillion dollars of healthcare expense by 2050. This project develops ways to accelerate the development of one of the only known effective alternatives to chemical-based antibiotics: bacteriophages. These micro-organisms are all around us, the most abundant form of life on the planet, and are highly evolved to eliminate specific bacteria. But this abundance, and our own immune systems, also make them challenging to achieve effectiveness at scale. This project tackles some of these challenges. The proposed project has the goal of developing a rapid and efficient parametric model for predicting the likelihood that a given phage will be able to survive sufficiently long in the presence of an active immune system that they may be effective as a treatment against their target bacterial infection. The basis for this project was the recent discovery that phage thought to be broadly similar could have vastly different average lifetimes in the blood of mice. Review of the literature revealed that very little prior work had been done to attempt to characterize phages based on this in-blood lifetime, or persistence. While persistence can be measured for a given phage by using animal models, this is a time-consuming and expensive approach that is difficult to scale. This project will simultaneously gather physical parameters and in-vivo persistence measures using mice models for 400 phage. The resultant data will then be analyzed to develop a parametric, predictive, statistical model that can be applied to a broad category of phage to obtain persistence likelihood without the time, effort, and expense of using animal models. 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.