Phage-mediated horizontal transfer of virulence genes with regulatory feedback from the host.

Phage-mediated horizontal transfer of virulence genes can enhance the transmission and pathogenicity of (), a process potentially regulated by its regulatory mechanisms. In this study, we explored the global dynamics of phage-mediated horizontal transfer in and investigated the role of its regulatory mechanisms in transduction. A total of 5178 viral sequences encoding 12 virulence genes were retrieved from the Integrated Microbial Genomes and Virome (IMG/VR) database, alongside 466,136 genomes from EnteroBase. Virulence genes, including (acyl carrier protein), (P-type Mg transporter), (autotransporter porin), and (flagellar filament protein), were widely distributed in phages and across North America, Europe, and Asia. Phylogenetic analysis revealed close genetic affinity between phage- and bacterial-encoded virulence genes, suggesting shared ancestry and historical horizontal gene transfer events. The global regulator carbon storage regulator A () was highly conserved and ubiquitous in . Overexpression of inhibited prophage cyclization and release by upregulating the prophage repressor during horizontal gene transfer. Overall, these findings enhance our understanding of phage-mediated horizontal transfer of virulence genes, explore new areas of bacterial regulators that inhibit gene exchange and evolution by affecting phage life cycles, and offer a novel approach to controlling the transmission of phage-mediated virulence genes.