Plasmid-Specific Bacteriophages to mitigate the Spread of Antimicrobial Resistance in Used Water & the Environment (Phage POWER).

Antimicrobial resistance (AMR) is a global public health concern that forebodes a dramatic scenario for the coming decades.

This crisis is worsened by the ability of antimicrobial-resistant bacteria to spread their antimicrobial resistance genes (ARGs) between and within microbial communities by horizontal transfer, and especially by conjugation in wastewater environments. Therefore, these environments are hotspots and potential control points in the spread of clinically relevant ARGs.

Viruses that attack plasmid-bearing bacteria via plasmid-encoded structures have been described.

They were mainly isolated several decades ago where they were instrumental in understanding plasmid biology, but many of them are no longer available and have not been documented comprehensively.

It has been demonstrated that they reduce the rate of conjugation in pure culture studies; however, their effect in microbial communities is still unknown.

Can we leverage some of these natural ‘enemies’ of plasmids to mitigate the spread of AMR in the diverse microbial communities that are typical of biological water treatment? Can we fight evolution with evolution? This is the ambition of this proposal.

The research will be divided into four packages: plasmid collection, phage isolation, phage characterization and phage efficiency assessment. Plasmids involved in the epidemic dissemination of carbapenem and multiple antibiotic resistance will be studied.

Phages will fluorescently labelled and used to measure the reduction in transfer rate of ARGs in environmental bacterial communities by fluorescence activated cell sorting.

The multidisciplinary nature of the project is strong, involving a combination of environmental microbiology, molecular biology, metagenomics and virology.

This innovative approach will increase the skills of the experienced researcher, both research-related and transferable ones, leading to improved career prospects, and contributing to solving the global crisis of AMR.