SBIR Phase II:Polyvalent Bacteriophages as Livestock Feed Additives and Alternatives to Antibiotics for Pathogen Control and Improved Animal Performance

这个小企业创新研究（SBIR）第二阶段项目的更广泛影响将是减轻抗生素耐药性细菌的传播。在美国，抗生素耐药性估计每年导致200多万人患病，23，000人死亡，花费550亿美元。在全球范围内，它每年导致70万人死亡，并通过对收入，生产力，投资和医疗成本的影响使全球国内生产总值减少约1.5%。在一些国家，动物部门占抗生素消费量的80%。然而，抗生素饲料添加剂广泛用于养牛业，因为它们通过降低肝脏疾病的发生率和严重程度提供了显着的经济和动物福利效益。由于该行业的利润率已经很低，撤回抗生素饲料添加剂对许多生产商来说可能是财务灾难，并可能导致供应链中断。该项目通过开发一种具有成本效益的抗生素饲料添加剂替代品，为肉牛业提供解决方案。拟议项目旨在开发一种基于噬菌体的饲料添加剂，以抑制牛肝脓肿的主要病原体坏死梭杆菌的生长，并减少或消除饲养场牛对抗生素饲料添加剂的需求。第一个项目目标是将温和噬菌体库转化为专性裂解突变体，以增强其对牛瘤胃中坏死梭杆菌的长期抑制的适用性。第二个目标是优化和扩大这些噬菌体的生产，并开发一种可以容易地整合到牛口粮中的产品配方。最终目标是进行喂养试验，以优化剂量要求，并获得体内的疗效证明。该奖项反映了NSF的法定使命，并已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。

The broader impact of this Small Business Innovation Research (SBIR) Phase II project will be to mitigate the spread of antibiotic resistant bacteria. In the United States, antibiotic resistance is estimated to cause over 2 million illnesses, 23,000 deaths, and cost $55 billion annually. Worldwide, it causes 700,000 deaths annually, and reduces global gross domestic product by approximately 1.5% through its impact on income, productivity, investment and healthcare costs. The animal sector accounts for up to 80% of antibiotic consumption in some countries. However, antibiotic feed additives are widely used in the cattle industry because they provide significant economic and animal welfare benefits by reducing the incidence and severity of liver abscesses. As the industry already operates on narrow profit margins, withdrawing antibiotic feed additives may be financially catastrophic for many producers, and could lead to supply chain disruption. This project provides a solution to the beef cattle industry through development of a cost-effective alternative to antibiotic feed additives.The proposed project aims to develop a bacteriophage-based feed additive to inhibit the growth of the primary etiologic agent of bovine liver abscesses, Fusobacterium necrophorum, and reduce or eliminate the need for antibiotic feed additives in feedlot cattle. The first project objective is to convert a library of temperate bacteriophages to obligately lytic mutants to enhance their suitability for long-term inhibition of Fusobacterium necrophorum in cattle rumen. The second objective is to optimize and scale up production of these bacteriophages and develop a product formulation that can be readily integrated into cattle rations. The final objective is to conduct feeding trials to optimize dosing requirements and obtain in vivo proof of efficacy.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.