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性病原体对 ** 农业和食品工业具有重大和全球性的影响。细菌对抗菌剂的耐药性增加，由于抗菌剂耐药性增加的可能性，** 抗生素在畜禽中的使用受到质疑。因此，需要在食品生产链中采取替代战略来对付细菌性病原体。裂解性噬菌体（Lytic bacteriophage，缩写为BPHs）是一种细菌特异性病毒，能够裂解并杀死目标细菌。SyntBioLab Inc.是开发应用程序来控制细菌 ** 病原体通过使用杀虫剂。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，鸟类病原性大肠杆菌。大肠杆菌（APEC）是呼吸道和全身感染的主要原因。有许多类型的E。大肠杆菌菌株感染家禽，因此，这是一个挑战 **，彻底的特点，将有广谱活性，对多种亚太经合组织。在 ** NSERC Engage赠款期间，我们从环境样品中分离出溶解性微生物。我们证明了某些抗生素对多种APEC菌株具有广泛的杀伤活性。本提案的目的是 ** 通过确定减少接种特定APEC菌株 ** 的雏鸡定植的有效性，继续表征这些病毒。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表征这些噬菌体。该项目将与合作伙伴SyntBioLab Inc.密切合作 **，结合我们在致病性大肠杆菌方面的专业知识大肠杆菌和鸡 ** 实验模型和SyntBioLab Inc.的优势，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抗生素，并可以 ** 减少一些不同的APEC菌株的定殖。减少了E.粪便中的大肠杆菌会降低来自粪便和垃圾尘的呼吸道大肠杆菌病的风险。这种噬菌体可以减少APEC感染，提高家禽产量，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.