SBIR Phase I: 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）项目的更广泛的影响/商业潜力是开发一种有效和可持续的替代动物饲料中使用的抗生素和杀菌剂，这将有助于减轻多重耐药细菌对全球健康的威胁。肉牛行业正面临越来越大的监管和公众压力，要求减少或消除抗生素饲料添加剂的使用，因为它们被认为是推动耐药性细菌扩散的主要因素。然而，饲用抗生素通过降低肝脏疾病的发生率和严重程度，为养牛业提供了显著的经济和动物福利效益。该项目通过提供一种具有成本效益的替代饲用抗生素的方法，为这些相互冲突的问题提供了一种替代方案。此外，随着对瘤胃微生物组如何影响动物生理和性能的充分了解，这项技术可以很容易地适应于选择性地靶向降低动物生长或饲料效率或产生甲烷的微生物物种，从而提高畜牧业的经济和环境可持续性。该SBIR I期项目建议开发一种低剂量的基于噬菌体的饲料添加剂，该添加剂可以通过免疫施用来控制牛瘤胃中致病性坏死梭杆菌的生长。F.坏死菌是谷物喂养的牛中肝脓肿的病原体，目前在饲料中添加抗生素以防止其生长并限制脓肿的发生。然而，饲用抗生素促进抗生素耐药菌的增殖，并可能对瘤胃微生物组造成不良的脱靶效应。本研究旨在开发广泛的宿主范围（多价）噬菌体作为控制牛病原体的经济手段。将使用专门的方法分离多价噬菌体，该方法基于瘤胃微生物组成选择具有预定宿主范围的噬菌体。然后将在模拟牛瘤胃的生物反应器中对每种噬菌体进行表征和功效测试。将配制噬菌体混合物并测试其最小化噬菌体抗性发展的能力。这项研究的预期成果是建立一个多价噬菌体库，可以有效地控制F。该奖项反映了NSF的法定使命，并被认为是值得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的支持。

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. 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.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.