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.