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

SBIR 第二阶段：多价噬菌体作为牲畜饲料添加剂和抗生素替代品，用于病原体控制和改善动物生产性能

• 批准号: 2025980
• 负责人: Jacques Mathieu
• 金额: $ 99.99万
• 依托单位: Sentinel Environmental Group LLC
• 依托单位国家: 美国
• 项目类别: Cooperative Agreement
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-09-15 至 2023-11-30
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=2025980&HistoricalAwards=false
• 关键词: SBIR; Phase; II; Polyvalent; Bacteriophages

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.

这项小企业创新研究（SBIR）第二阶段项目的更广泛影响将是减轻抗生素耐药细菌的传播。在美国，抗生素耐药性估计导致200多万人患病，23,000人死亡，每年造成550亿美元的损失。在世界范围内，它每年造成70万人死亡，并通过对收入、生产力、投资和医疗保健费用的影响，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，抗生素饲料添加剂被广泛应用于养牛业，因为它们通过降低肝脓肿的发生率和严重程度，提供了显著的经济效益和动物福利。由于该行业的利润率已经很低，取消抗生素饲料添加剂对许多生产商来说可能是一场经济灾难，并可能导致供应链中断。该项目通过开发具有成本效益的抗生素饲料添加剂替代品，为肉牛行业提供了解决方案。该项目旨在开发一种以噬菌体为基础的饲料添加剂，以抑制牛肝脓肿的主要病原——坏死梭杆菌的生长，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一个温带噬菌体库转化为专性裂解突变体，以提高它们对牛瘤胃中坏死梭杆菌的长期抑制能力。第二个目标是优化和扩大这些噬菌体的生产，并开发一种易于融入牛口粮的产品配方。最终目标是进行饲养试验，以优化剂量要求并获得体内有效性证明。该奖项反映了美国国家科学基金会的法定使命，并通过使用基金会的知识价值和更广泛的影响审查标准进行评估，被认为值得支持。

项目成果

Unexpected finding of Fusobacterium varium as the dominant Fusobacterium species in cattle rumen: potential implications for liver abscess etiology and interventions

意外发现变异梭杆菌作为牛瘤胃中的优势梭杆菌：对肝脓肿病因和干预措施的潜在影响

• DOI: 10.1093/jas/skad130
• 发表时间: 2023
• 期刊: Journal of Animal Science
• 影响因子: 3.3
• 作者: Schwarz, Cory;Mathieu, Jacques;Gomez, Jenny Laverde;Miller, Megan R.;Tikhonova, Marina;Nagaraja, Tiruvoor. G.;Alvarez, Pedro J. J.
• 通讯作者: Alvarez, Pedro J. J.

Renaissance for Phage-Based Bacterial Control

• DOI: 10.1021/acs.est.1c06232
• 发表时间: 2022-04-19
• 期刊: ENVIRONMENTAL SCIENCE & TECHNOLOGY
• 影响因子: 11.4
• 作者: Schwarz, Cory;Mathieu, Jacques;Alvarez, Pedro J. J.
• 通讯作者: Alvarez, Pedro J. J.