Project: Novel interventions for eliminating one-health mobile antimicrobial resistance genes from human and animal microbiomes

Acronym MOB-TARGET (Reference Number: JPIAMR_2021_P004)
Duration 01/05/2022 - 30/04/2025
Project Topic The most important cases of one-health antimicrobial resistance (AMR) are caused by dissemination of antibiotic resistance genes on mobile genetic elements. In this project, 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. SSAs will include CRISPR-Cas9 systems that will target AMR plasmids, “killer cassettes” that will kill bacteria carrying mobile integrons that are key platforms for AMR, and 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 LMICs, but the chicken gut microbiome acts as a reservoir of AMR that can be transmitted to humans. First, we will develop pilus-dependent lytic phage (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.
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Call 1st JPIAMR-ACTION Joint Call 2021

Project partner

Number Name Role Country
1 University of Oxford Coordinator United Kingdom
2 University of Manchester Partner United Kingdom
3 Centro Nacional de Biotecnología Partner Spain
4 Universidad Complutense Partner Spain
5 Max von Pettenkofer-Institute, LMU Munich Partner Germany
6 Institut Pasteur Partner France
7 Jiangsu Academy of Agricultural Sciences Partner China