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




Research Project: 2022-01-04 - 2025-03-31
Total sum awarded: €1 403 468

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 and 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.

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  • Ulrich Dobrindt, Universitätsklinikum Münster, Germany (Coordinator)
  • Clara Marín-Orenga, Universidad Cardenal Herrera - CEU, Spain (Partner)
  • Muna Anjum, Animal and Plant Health Agency, United Kingdom (Partner)
  • Raul Fernandez Lopez, Universidad de Cantabria, Spain (Partner)
  • Danish Malik, Loughborough University, United Kingdom (Partner)
  • Annamária Szmolka, Veterinary Medical Research Institute, Hungary (Partner)
  • Eliora Ron, Tel-Aviv University, Israel (Partner)

The spread of multi-drug resistant (MDR) bacteria in food-producing animals including broilers is a global public health concern. Controlling growth of MDR bacteria and limiting the transmission of antimicrobial resistance genes in broilers could be an effective mitigation strategy. To counteract the spread of MDR bacteria among zoonotic pathogens in food-producing animals and reduce the risk of their transmission to humans or the environment, antibiotic use in animal husbandry has to be reduced. Bacteriophage therapy is increasingly accepted as an environmentally-friendly antimicrobial intervention strategy, effective at specifically targeting bacterial pathogens, to prevent the transmission of resistant bacteria from foods to humans and vice versa. We use MDR Salmonella and E. coli in broilers as a model and will first select the most efficient phage combinations to specifically reduce these bacteria and MDR plasmids in broilers. Using laboratory, an experimental chicken gut model and farm-level experiments, we will then establish the efficacy of phage formulations as feed additives within a commercial farming context to reduce bacterial numbers and progressively reduce MDR plasmid carriage in broilers. We will test the effect of phage therapy on intestinal parameters of the treated broilers and also on the broiler intestinal microbiome and resistome composition. We will investigate the transmission of AMR plasmids between different enterobacteria in the broiler gut and improve on-site detection of MDR foodborne pathogens as an early warning system at farm level.