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

从单一健康角度减少抗菌素耐药性肠杆菌传播的噬菌体疗法

• 批准号: MR/W031248/1
• 负责人: Danish Malik
• 金额: $ 61.53万
• 依托单位: Loughborough University
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2022
• 资助国家: 英国
• 起止时间: 2022 至 无数据
• 项目状态: 未结题
• 来源: https://gtr.ukri.org/projects?ref=MR%2FW031248%2F1
• 关键词: Phage; Therapy; Reduce; AMR; Enterobacteria

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.

“一个健康”的方法认识到人类和动物健康与环境的密切联系。多重耐药（MDR）病原体，如沙门氏菌和大肠杆菌。家禽和相关食品中的大肠杆菌正日益成为全球公共卫生问题。必须减少畜牧业中抗生素的使用，以抵消食品动物中人畜共患病原体中耐药质粒的传播以及耐药细菌传播给人类和环境的风险。我们将展示基于噬菌体的干预措施的潜力，以控制和减少商业农场环境中肉鸡中耐药人畜共患病原体的发生率及其释放到环境水库中。通过动物饲料使用先进的靶向噬菌体递送系统将影响减少MDR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引物将有助于选择性靶向携带MDR质粒的细菌，而不会显著影响整体肠道微生物组组成。我们将研究耐药质粒在大肠杆菌中的循环和噬菌体治疗的效果，首先使用一种新的离体鸡肠道模型，然后在养鸡场。为了早期发现、评估治疗或预防MDR沙门氏菌或大肠杆菌的传播。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，用于确定接合质粒、抗生素抗性基因和毒力标记的存在。