Molecular drivers of fusion plasmid: mechanistic insights and evolutionary implications

Plasmid fusion, the recombination of distinct plasmids into a single plasmid, constitutes a critical mechanism shaping bacterial evolution. This process facilitates genetic resource consolidation, enabling bacterial populations to rapidly adapt to selective pressures such as antibiotic exposure. The growing recognition of plasmid fusion as a widespread genomic recombination event necessitates a comprehensive analysis of its prerequisites, molecular mechanisms, and functional consequences. This review synthesizes current knowledge on the triggers, molecular mechanisms, and outcomes of plasmid fusion. We demonstrate that conjugative transfer and antibiotic selection pressure drive plasmid fusion via DNA double-strand breaks and SOS response activation, with formation mechanisms dominated by insertion sequence-mediated homologous recombination or transposon-mediated recombination. Fusion plasmids amplify antimicrobial resistance (AMR) dissemination by creating multidrug-resistant megaplasmids, enable cross-host transfer of non-conjugative plasmids, and foster virulence-resistance hybrid elements. Furthermore, we propose a novel framework for investigating, specifically addressing how fusion plasmids achieve compensatory mechanisms to balance functional redundancies among critical genetic modules. Elucidating the evolutionary drivers underlying the pervasive dissemination of fusion plasmids will not only advance our understanding of their ecological success but also identify critical intervention targets to disrupt their dissemination.