The broader impact/commercial potential of this Small Business Innovation Research (SBIR) project is the development of an effective and sustainable alternative to antibiotics and biocides used in animal feed, which will help mitigate the global health threat of multidrug-resistant bacteria. The beef cattle industry is under increasing regulatory and public pressure to reduce or eliminate the use of antibiotic feed additives as they are considered a major factor driving the proliferation of antibiotic-resistant bacteria. However, in-feed antibiotics provide significant economic and animal welfare benefits to the cattle industry by reducing the incidence and severity of liver abscesses. This project provides an alternative for these conflicting concerns by providing a cost-effective alternative to in-feed antibiotics. Further, with sufficient understanding of how the rumen microbiome impacts animal physiology and performance, this technology could be easily adapted to selectively target microbial species that reduce animal growth or feed efficiency, or that produce methane, increasing the economic and environmental sustainability of livestock agriculture. <br/><br/>This SBIR Phase I project proposes to develop a low-dose, bacteriophage-based feed additive that can be prophylactically administered to control the growth of pathogenic Fusobacterium necrophorum in cattle rumen. F. necrophorum is a causative agent of liver abscesses in grain-fed cattle, and antibiotics are currently added to feed to prevent its growth and limit abscess occurrence. However, in-feed antibiotics promote the proliferation of antibiotic resistant bacteria, and can cause undesirable off-target effects to the rumen microbiome. This research seeks to develop broad host-range (polyvalent) bacteriophages as an economical means of controlling cattle pathogens. Polyvalent bacteriophages will be isolated using specialized methods that select for those with a predetermined host-range based on rumen microbial composition. Each bacteriophage will then be characterized and tested for efficacy within a bioreactor operated to simulate the cattle rumen. Bacteriophage cocktails will be formulated and tested for their ability to minimize the development of bacteriophage resistance. The expected outcome of the proposed research is a library of polyvalent bacteriophages that can effectively control F. necrophorum under rumen-like conditions, and which will be further tested in animal studies.<br/><br/>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.