Novel interventions for eliminating one-health mobile antimicrobial resistance genes from human and animal microbiomes (MOB-TARGET)



Many of the most important one-health AMR genes are carried on mobile genetic elements that move between bacterial strains through the process of conjugation. The genetic mobility of these AMR genes allows them to become widely disseminated across species of bacteria, including harmless commensal strains and dangerous pathogen strains, and ecological niches, including humans, farms and the environment.

In our project, we will develop a series of novel interventions to combat these mobile resistance genes. First, we will develop novel genetic tools that will destroy plasmids carrying resistance genes and selectively kill AMR bacteria. In many regions of the world, infants are commonly colonised with AMR bacteria, complicating the treatment of dangerous infections, such as neonatal sepsis. We will test the ability of our genetic tools to eradicate AMR from the neonatal microbiome using experiments in mice containing a microbiome that is typical of human infants.

Some phage (viruses that infect bacteria) infect and kill bacteria that carry conjugative plasmids. We will test the ability of both phage and novel genetic tools to eliminate AMR from the gut microbiome of chickens. Chickens provide a key source of animal protein (global production is about 120 million tonnes per year), but chickens act as an important source of AMR bacteria that can transfer to humans through food and through the use of chicken manure as a fertiliser.

This two pronged approach will allow us to reduce the transmission of AMR to humans and to eliminate AMR from a high risk human population.

Project partners

  • Craig MacLean, University of Oxford, United Kingdom (Coordinator)
  • Michael Brockhurst, University of Manchester, United Kingdom
  • Alvaro San Millan, Centro Nacional de BiotecnologĂ­a, Spain
  • Jose Antonio Escudero, Universidad Complutense, Spain
  • Bärbel Stecher-Letsch, Max von Pettenkofer-Institute, LMU Munich, Germany
  • Didier Mazel, Institut Pasteur, France
  • Tao He, Jiangsu Academy of Agricultural Sciences, China