Evolution in Quantum Leaps: Multiple Combinatorial Transfers of HPI and Other Genetic Modules in <em>Enterobacteriaceae</em>

<div><p>Horizontal gene transfer is a key step in the evolution of <em>Enterobacteriaceae</em>. By acquiring virulence determinants of foreign origin, commensals can evolve into pathogens. In <em>Enterobacteriaceae</em>, horizontal transfer of these virulence determinants is largely dependent on transfer by plasmids, phages, genomic islands (GIs) and genomic modules (GMs). The High Pathogenicity Island (HPI) is a GI encoding virulence genes that can be transferred between different <em>Enterobacteriaceae</em>. We investigated the HPI because it was present in an <em>Enterobacter hormaechei</em> outbreak strain (EHOS). Genome sequence analysis showed that the EHOS contained an integration site for mobile elements and harbored two GIs and three putative GMs, including a new variant of the HPI (HPI-ICE<em>Eh1</em>). We demonstrate, for the first time, that combinatorial transfers of GIs and GMs between <em>Enterobacter cloacae</em> complex isolates must have occurred. Furthermore, the excision and circularization of several combinations of the GIs and GMs was demonstrated. Because of its flexibility, the multiple integration site of mobile DNA can be considered an integration hotspot (IHS) that increases the genomic plasticity of the bacterium. Multiple combinatorial transfers of diverse combinations of the HPI and other genomic elements among <em>Enterobacteriaceae</em> may accelerate the generation of new pathogenic strains.</p></div>