Genomic and functional characterisation of IncX3 plasmids encoding bla(SHV-12) in Escherichia coli from human and animal origin

The bla(SHV-12) beta-lactamase gene is one of the most prevalent genes conferring resistance to extended-spectrum beta-lactams in Enterobacteriaceae disseminating within and between reservoirs, mostly via plasmid-mediated horizontal gene transfer. Yet, studies regarding the biology of plasmids encoding bla(SHV-12) are very limited. In this study, we revealed the emergence of IncX3 plasmids alongside IncI1 alpha/beta in bla(SHV-12) in animal-related Escherichia coli isolates. Four representative bla(SHV-12)-encoding IncX3 plasmids were selected for genome sequencing and further genetic and functional characterization. We report here the first complete sequences of IncX3 plasmids of animal origin and show that IncX3 plasmids exhibit remarkable synteny in their backbone, while the major differences lie in their bla(SHV-12)-flanking region. Our findings indicate that plasmids of this subgroup are conjugative and highly stable, while they exert no fitness cost on their bacterial host. These favourable features might have contributed to the emergence of IncX3 amongst SHV-12-producing E. coli in the Netherlands, highlighting the epidemic potential of these plasmids.