Antibiotic resistance gene integration in ST38 Escherichia coli

Plasmids carrying antibiotic resistance genes (ARG) are the main mechanism of resistance acquisition and dissemination in Enterobacterales. However, the fitness-resistance tradeoff 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 Escherichia coli from the sequence type (ST) 38, most ARGs are chromosomally integrated. Here we reproduce by experimental evolution the move of blaOXA-48 from the pOXA-48 plasmid into the chromosome. We demonstrate that it depends on a high plasmid-induced fitness cost, on a mobile genetic structure embedding the ARG and on a host factor actively involved in pOXA-48 destabilization.