Phage-ICE tandems facilitate bacterial adaptation and antimicrobial resistance spread

Abstract

Phages and integrative and conjugative elements (ICEs) drive bacterial evolution, but how their interplay shapes bacterial adaptation and antimicrobial resistance (AMR) dissemination remains unclear. Here, we characterize phage-ICE tandems formed by site-specific accretion of phages and ICEs into cotransferable units. In Streptococcus , phage-encoded integrases (IntIE Phage ) drive stress-inducible excision and circularization, after which ICE machinery mediates conduction of the tandem. When excision is impaired, phage and phage-ICE fragments disseminate by transformation and integrate via RecA-dependent homologous recombination (HR), providing a fail-safe route. This pathway enables cotransfer of flanking chromosomal DNA, generating length-variable integrations that remodel transcriptional programs and increase oxidative stress tolerance. A global screen identified 612 phage-ICE tandems across seven phyla and 135 species, including multidrug-resistant pathogens, with lineage-specific repertoires of AMR, virulence, and metabolic genes. Rather than a hybrid element, these structures represent functional interplay where prophages exploit ICE conjugation while facilitating mobilization of the composite region. By coupling excision, transfer, and recombination, phage-ICEs shape adaptation and accelerate AMR spread.