Subinhibitory antibiotic concentrations promote the excision of a genomic island carried by the globally spread carbapenem-resistant Klebsiella pneumoniae sequence type 258

The ICEKp258.2 genomic island (GI) has been proposed as an important factor for the emergence and success of the globally spread carbapenem-resistant sequence type (ST) 258. However, a characterization of this horizontally acquired element is lacking. Using bioinformatic and experimental approaches, we found that ICEKp258.2 is not confined to ST258 and ST512, but also carried by ST3795 strains and emergent invasive multidrug-resistant pathogens from ST1519. We also identified several ICEKp258.2-like GIs spread among different STs, other species and even other pathogen genera, uncovering horizontal gene transfer events between different STs and bacterial genera. Also, the comparative and phylogenetic analyses of the ICEKp258.2-like GIs revealed that the most closely related ICEKp258.2-like GIs were harboured by ST11 strains. Importantly, we found that subinhibitory concentrations of antibiotics used in treating infections can induce the excision of this GI and modulate its gene expression. Our findings provide the basis for the study of ICEKp258.2 and its role in the success of ST258. They also highlight the potential role of antibiotics in the spread of ICEKp258.2-like GIs among bacterial pathogens.