Characterization of an IncFII Plasmid Encoding NDM-1 from Escherichia coli ST131

Background: The current spread of the gene encoding the metallo-beta-lactamase NDM-1 in Enterobacteriaceae is linked to a variety of surrounding genetic structures and plasmid scaffolds. Methodology: The whole sequence of plasmid pGUE-NDM carrying the bla(NDM-1) gene was determined by high-density pyrosequencing and a genomic comparative analysis with other bla(NDM-1)-negative IncFII was performed. Principal Findings: Plasmid pGUE-NDM replicating in Escherichia coli confers resistance to many antibiotic molecules including beta-lactams, aminoglycosides, trimethoprim, and sulfonamides. It is 87,022 bp in-size and carries the two beta-lactamase genes bla(NDM-1) and bla(OXA-1), together with three aminoglycoside resistance genes aacA4, aadA2, and aacC2. Comparative analysis of the multidrug resistance locus contained a module encompassing the bla(NDM-1) gene that is actually conserved among different structures identified in other enterobacterial isolates. This module was constituted by the bla(NDM-1) gene, a fragment of insertion sequence ISAba125 and a bleomycin resistance encoding gene. Significance: This is the first characterized bla(NDM-1)-carrying IncFII-type plasmid. Such association between the bla(NDM-1) gene and an IncFII-type plasmid backbone is extremely worrisome considering that this plasmid type is known to spread efficiently, as examplified with the worldwide dissemination of bla(CTX-M-15)-borne IncFII plasmids.