Characterizing lytic bacteriophages against pathogenic E. coli: killing spectrum, efficacy in vivo, and genomic analysis

对动物健康和食品安全具有重要意义的细菌病原体对**农业和食品工业有重大的全球影响。细菌对抗菌剂的抗药性有所增加，家畜和家禽中抗生素的使用受到质疑，因为可能会增加抗菌素的抗药性。因此，需要采取替代策略来应对食品生产链中的细菌病原体。裂解噬菌体(噬菌体)是细菌特有的病毒，可以裂解和杀死它们的目标细菌。SyntBioLab Inc.的重点之一是开发利用噬菌体控制细菌病原体的应用程序。大肠杆菌是食品安全和动物健康的主要问题。特别是，**在家禽(鸡和火鸡)中，禽类致病性大肠杆菌(APEC)是呼吸道和**系统感染的主要原因。有许多类型的大肠杆菌菌株感染家禽，因此，彻底鉴定对多种APEC具有广谱活性的噬菌体是一个挑战**。在**NSERC Engage拨款期间，我们从环境样本中分离了裂解噬菌体。我们证明了某些噬菌体对各种APEC菌株具有广泛的杀灭活性。这项建议的目的是**通过确定减少接种特定APEC菌株的幼鸡的有效性来**继续对这些噬菌体进行表征。我们还计划通过基因组测序、比较基因组学和电子显微镜进一步鉴定这些噬菌体。该项目将与合作伙伴SyntBioLab Inc.**密切合作，将我们团队在致病性大肠杆菌和鸡**实验模型方面的专业知识与SyntBioLab Inc.的优势相结合，包括比较基因组学和**生物信息学。该项目的总体目的是建立最强大和最有效的噬菌体，并可以**减少一些不同APEC菌株的定植。减少粪便中的大肠杆菌数量将**降低由粪便和垃圾灰尘引起的呼吸道大肠杆菌病的风险。这种噬菌体可以**减少APEC感染，改善家禽生产，并减少抗生素的使用来治疗此类感染。

Bacterial pathogens of importance to animal health and food safety have major and global impacts on**agriculture and food industries. There has been an increase in bacterial resistance to antimicrobials, and**antibiotic use in livestock and poultry has been questioned due to likelihood of increased antimicrobial**resistance. Alternative strategies to contend with bacterial pathogens within the food production chain are**therefore needed. Lytic bacteriophages (phages) are bacteria-specific viruses that can lyse and kill their**bacterial targets. One of the focuses of SyntBioLab Inc. is to develop applications to control bacterial**pathogens by using phages. Escherichia coli is a major problem for food safety and animal health. In particular,**in poultry (chickens and turkeys), avian pathogenic E. coli (APEC) is the predominant cause of respiratory and**systemic infection. There are numerous types of E. coli strains that infect poultry, and it is therefore a challenge**to thoroughly characterize phages that will have broad-spectrum activity against a diversity of APEC. During**the NSERC Engage grant, we isolated lytic phages from environmental samples. We demonstrated that certain**phages have a broad killing activity against a variety of APEC strains. The purpose of this proposal is to**continue characterization of these phages by determining efficacy to reduce colonization of young chicks**inoculated with specific APEC strains. We also plan on further characterizing these bacteriophages by genome**sequencing and comparative genomics and electron microscopy. This project will be in close collaboration**with the partner, SyntBioLab Inc., by combining our group's expertise in pathogenic E. coli and chicken**experimental models and the strengths of SyntBioLab Inc., including comparative genomics and**bioinformatics. The overall purpose of the project is to establish the most robust and effective phages and can**reduce colonization of a number of different APEC strains. Reduced numbers of E. coli from feces would**lower the risk of respiratory colibacillosis originating from feces and litter dust. Such bacteriophages could**reduce APEC infections, improve poultry production, and decrease antibiotic usage to treat such infections.