Plasmids carrying antibiotic resistance genes (ARG) are the main mechanism of resistance dissemination in Enterobacterales. However, the fitness-resistance trade-off may result in their elimination. Chromosomal integration of ARGs preserves resistance advantage while relieving the selective pressure for keeping costly plasmids. In some bacterial lineages, such as carbapenemase producing sequence type ST38 Escherichia coli, most ARGs are chromosomally integrated. Here we reproduce by experimental evolution the mobilisation of the carbapenemase bla_OXA-48 gene from the pOXA-48 plasmid into the chromosome. We demonstrate that this integration depends on a plasmid-induced fitness cost, a mobile genetic structure embedding the ARG and a novel antiplasmid system ApsAB actively involved in pOXA-48 destabilization. We show that ApsAB targets high and low-copy number plasmids. ApsAB combines a nuclease/helicase protein and a novel type of Argonaute-like protein. It belongs to a family of defense systems broadly distributed among bacteria, which might have a strong ecological impact on plasmid diffusion.

携带抗生素抗性基因（ARG）的质粒是肠杆菌科细菌耐药性传播的主要机制。然而，适应性与阻力的权衡可能会导致它们被淘汰。 ARG 的染色体整合保留了抗性优势，同时减轻了保留昂贵质粒的选择压力。在一些细菌谱系中，例如产生碳青霉烯酶的序列型 ST38大肠杆菌，大多数 ARG 是在染色体上整合的。在这里，我们通过实验进化重现了碳青霉烯酶bla _OXA-48基因从 pOXA-48 质粒到染色体中的动员。我们证明这种整合取决于质粒诱导的适应性成本、嵌入 ARG 的可移动遗传结构以及积极参与 pOXA-48 不稳定的新型抗质粒系统 ApsAB。我们证明 ApsAB 靶向高拷贝数和低拷贝数质粒。 ApsAB 结合了核酸酶/解旋酶蛋白和新型 Argonaute 样蛋白。它属于广泛分布在细菌中的防御系统家族，可能对质粒扩散产生强烈的生态影响。