Antiviral defense systems drive persistence of antimicrobial‐resistant bacteria but limit the transfer of antimicrobial resistance genes in anaerobic digestion

Phage-host interactions critically shape environmental antimicrobial resistance (AMR). Using swine manure anaerobic digestion and multi-omics (metagenomics, meta-transcriptomics, and Hi-C), we mapped the phage-bacteria arms race and its impact on AMR dynamics. We revealed that phage-mediated lysis overwhelmingly dominates transduction, while phages rarely carry antimicrobial resistance genes (ARGs), and phage-borne ARGs showed no expression, challenging the paradigm of phages as primary vectors of ARGs. Crucially, the intense on-going phage-host arms race drives the widespread presence and expression of antiviral defense systems (ADSs) in antimicrobial-resistant bacteria (ARB). These ADSs exhibit a vital ecological dual role: they protect ARBs from phage lysis promoting persistence while simultaneously suppressing horizontal gene transfer (HGT, e.g., conjugation), as validated by in vitro conjugation assays. Our findings elucidate this duality, offering a novel framework to harness phage lytic pressure and ADS-mediated HGT suppression for environmental AMR mitigation.