Evolutionary arms races dictate the boundaries of phage-mediated antimicrobial resistance transfer in priority pathogens

Here, we present a global pan-genomic analysis of the priority pathogens including 13,238 fecal coliform bacteria (FCB) and ESKAPEE alongside their 38,952 associated bacteriophages. We reveal a profound asymmetry in AMR reservoirs: while bacterial genomes are hyper-enriched with antimicrobial resistance genes (ARGs; averaging 45.9 copies per genome), viral carriage is rare (1.5%), with predicted phage-mediated transduction restricted to a mere 0.11% of the identified phage-host interactions.

This severe horizontal transfer bottleneck is dictated by a fierce evolutionary arms race. Host bacteria deploy massive antiviral defense systems (ADS, averaging 23.7 ADS per genome) that paradoxically collude to intercept exogenous ARG-bearing plasmids. We assumed that phages heavily prioritize anti-defense systems rather than passive ARGs shuttles.