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Horizontal gene transfer is a key step in the evolution of  Enterobacteriaceae . By acquiring virulence determinants of foreign origin, commensals can evolve into pathogens. In  Enterobacteriaceae , 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  Enterobacteriaceae . We investigated the HPI because it was present in an  Enterobacter hormaechei  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 Eh1 ). We demonstrate, for the first time, that combinatorial transfers of GIs and GMs between  Enterobacter cloacae  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  Enterobacteriaceae  may accelerate the generation of new pathogenic strains.

Evolution in Quantum Leaps: Multiple Combinatorial Transfers of HPI and Other Genetic Modules in Enterobacteriaceae