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.
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Huang et al. (2026) studied this question.
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