Diverse bacteriophages for biocontrol of ESBL- and AmpC-β-lactamase-producing E. coli

Novel solutions are needed to reduce the risk of transmission of extended spectrum β-lactamase and AmpC β-lactamase producing Escherichia coli (ESBL/AmpC E. coli) from livestock to humans. Given that phages are promising biocontrol agents, a collection of 28 phages that infect ESBL/AmpC E. coli were established. Whole genome sequencing showed that all these phages were unique and could be assigned to 15 different genera. Host range analysis showed that 82% of 198 strains, representing the genetic diversity of ESBL/AmpC E. coli, were sensitive to at least one phage. Identifying receptors used for phage binding experimentally as well as in silico predictions, allowed us to combine phages into two different cocktails with broad host range targeting diverse receptors. These phage cocktails efficiently inhibit the growth of ESBL/AmpC E. coli in vitro, thus suggesting the potential of phages as promising biocontrol agents.