MOB-TARGET
The most important cases of one-health antimicrobial resistance (AMR) are caused by dissemination of antibiotic resistance genes on mobile genetic elements. In the EU-funded consortium MOB-TARGET, we will develop novel interventions aimed at selectively eliminating mobile AMR from complex human and animal microbiomes. We will focus on two urgent AMR problems:
1. AMR poses a critical health risk to neonates. We will develop sequence specific antimicrobials (SSA) and conjugative delivery systems to eliminate AMR from the neonatal microbiome. These will include (1) CRISPR-Cas9 systems that will target AMR plasmids, (2) “killer cassettes” that will kill bacteria carrying mobile integrons that are key platforms for AMR, and (3) inducible toxin-intein antimicrobials that will kill cells carrying AMR plasmids. We will test the efficacy of these systems using in vitro and in vivo models of the neonatal human microbiome.
2. Chickens provide a key source of protein in low- and middle-income countries but the chicken gut microbiome acts as a reservoir of AMR that can be transmitted to humans. First, we will develop pilus-dependent lytic phages (PDB) as a tool to eliminate mobile ARGs. Second, we will test the ability of both SSAs and PDBs to control AMR in the chicken gut microbiome using in vivo experiments.
Our two-pronged approach will help eliminate AMR from a high-risk patient population and restrict the colonization of humans by decontaminating an important agricultural source of AMR.
Project Partners
- Craig MacLean, University of Oxford, United Kingdom (Coordinator)
- Michael Brockhurst, University of Manchester, United Kingdom
- Alvaro San Millan, Centro Nacional de Biotecnología, Spain
- Jose Antonio Escudero, Universidad Complutense, Spain
- Didier Mazel, Institut Pasteur, France
- Tao He, Jiangsu Academy of Agricultural Sciences, China