Investigating the role of novel alphatectiviruses in reducing carriage and transfer of antimicrobial resistance plasmids

OBJECTIVE: To identify suitable phage isolates and the characterization of factors that define their host range and interactions with bacteria, which are of major importance for optimizing their use in reducing antimicrobial resistance (AMR). METHODS: We characterized two novel conjugation apparatus-specific alphatectiviruses that target plasmids of the incompatibility groups IncW, N, and P. We show that ɸ4187/61 and ɸ4187/77 specifically target plasmid-harbouring bacteria in mixed bacterial populations, thereby reducing overall plasmid carriage and transfer. RESULTS: Occurring phage resistance was associated with plasmid loss or greatly reduced plasmid transfer efficiency, further supporting the desired reducing effect of phage treatment on AMR plasmid dissemination. The host range of the two alphatectiviruses was not only determined by the type of the plasmid-encoded conjugation apparatus but also by other properties related to the conjugative plasmid, bacterial host, or phage. Treatment of Galleria mellonella larvae force-fed with Escherichia coli MG1655 carrying plasmid RP4 with ɸ4187/77 significantly reduced the RP4 transfer frequency and total number of RP4-harbouring bacteria in the G. mellonella gut. CONCLUSIONS: Alphatectiviruses such as ɸ4187/61 and ɸ4187/77 are promising candidates for approaches to combat AMR by phage-dependent reduction of plasmid carriage and transfer.