Antibiotic resistance genes often situate in mobile genetic elements such as plasmids that readily disperse between different bacterial pathogens. The antibiotic resistance crisis is therefore largely a problem of plasmids. However, there are plasmid-dependent bacteriophages (phages), viruses infecting bacteria, that bind to plasmid-encoded features on bacterial cells. They have notable potential for applications: plasmid-dependent phages target especially antibiotic resistant bacteria, and their presence selects for the loss of resistance plasmid (i.e. they restore sensitivity to antibiotics). However, the currently available plasmid-dependent phages cover only a tiny fraction of known resistance plasmids. In the proposed project, we isolate new plasmid-dependent phages against common resistance plasmids and utilize artificial evolution to expand the host range of existing plasmid-dependent phages.

2022

2026