Phage Therapy to Reduce AMR Enterobacteria Spread from a One Health Perspective

“同一健康”方针确认了人类、动物健康和环境之间的密切联系。禽类和相关食品中的多药耐药(MDR)病原体，如沙门氏菌和大肠杆菌，正日益成为全球公共卫生问题。必须减少抗生素在畜牧业中的使用，以抵消MDR质粒在食品生产动物的人畜共患病原体之间的传播，以及MDR细菌向人类和环境传播的风险。我们将展示基于噬菌体的干预措施的潜力，以控制和减少商业养殖场环境中肉鸡的MDR人畜共患病病原体的发病率和释放到环境水库中。通过动物饲料使用先进的靶向噬菌体输送系统，将减少多药耐药细菌和相关质粒在肉鸡中的传播，并减少它们向人类或环境的传播。结合质粒编码的菌毛特异性噬菌体将有助于选择性地靶向携带多药耐药质粒的细菌，而不会显著影响肠道微生物群的整体组成。我们将首先使用一种新的体外鸡肠模型，然后在一个养鸡场上，研究多药耐药质粒在大肠杆菌肠杆菌之间的循环和噬菌体治疗的效果。为了及早发现、评估治疗或防止多药耐药沙门氏菌或大肠杆菌在肉鸡群中传播，我们将开发基于PCR/LAMP/CRISPR-CAS分析的简单易用的现场检测工具，以确定是否存在结合质粒、抗生素耐药性基因和毒力标记。

The 'One Health' approach recognises the close connection of human and animal health and the environment. Multidrug resistant (MDR) pathogens, e.g. Salmonella and E. coli in poultry and related foods are increasingly becoming a global public health concern. Antibiotic use in animal husbandry has to be reduced to counteract spread of MDR plasmids among zoonotic pathogens in food-producing animals and the risk of transmission of MDR bacteria to humans and the environment.We will demonstrate the potential of a bacteriophage-based intervention to control and reduce the incidence of MDR zoonotic pathogens in broilers in a commercial farm environment and their release into environmental reservoirs. The use of an advanced targeted phage delivery system via animal feed will impact on reduced spread of MDR bacteria and relevant plasmids in broilers as well as their transmission to humans or to the environment. Conjugative plasmid-encoded pilus-specific phages will help to selectively target MDR plasmid-carrying bacteria without markedly affecting the overall intestinal microbiome composition. We will study the circulation of MDR plasmids among coliform enterobacteria and the effects of phage therapy, by initially using a novel ex-vivo chicken gut model and then on a chicken farm. For early detection, assessment of treatment or prevention of spread of MDR Salmonella or E. coli in broiler flocks, we will develop easy to use on-site detection tools based on PCR/LAMP/CRISPR-Cas assays for determining the presence of conjugative plasmids, antibiotic resistance genes and virulence markers.