Plasmid dependent phage eliminate pathogenic bacteria and antibiotic resistance plasmids from the chicken gut microbiome

Conjugative plasmids are a key reservoir of antimicrobial resistance (AMR) in commensal and pathogenic bacteria within the gut microbiome. Plasmid-dependent phage (PDPs) are a promising therapeutic option directly targeting AMR plasmids, but the efficacy of PDP therapy in vivo is poorly understood. Here, we show that treatment with the PRD1 phage eliminated Salmonella enterica carrying a broad-host range IncP AMR plasmid (RP4) from the chicken gut microbiome. Moreover, PRD1 treatment prevented the transfer of the RP4 plasmid to other members of the gut microbiome, whilst causing only minimal disruption to microbiome composition. Our results demonstrate that PDP therapy rapidly eliminates AMR from a natural gut microbiome by killing pathogenic bacteria and blocking AMR plasmid transmission to commensals, highlighting the conjugative pilus as a promising antimicrobial target.