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

“同一个健康”方针认识到人类和动物健康与环境之间的密切联系。家禽及相关食品中的沙门氏菌和大肠杆菌等多重耐药病原体日益成为全球公共卫生关注的问题。必须减少畜牧业中抗生素的使用，以抵消耐多药质粒在食用动物的人畜共患病原体中的传播以及耐多药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在控制和减少商业农场环境中肉鸡耐多药人畜共患病原体发病率及其释放到环境水库中的潜力。通过动物饲料使用先进的靶向噬菌体传递系统将减少耐多药细菌和相关质粒在肉鸡中的传播，以及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MDR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型离体鸡肠道模型，然后在养鸡场研究耐多药质粒在大肠菌群肠杆菌中的循环和噬菌体治疗的效果。为了早期发现、评估耐多药沙门氏菌或大肠杆菌在肉鸡群中的传播，我们将开发基于PCR/LAMP/CRISPR-Cas检测的易于使用的现场检测工具，以确定共轭质粒、抗生素耐药基因和毒力标记的存在。

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.