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

Abstract

BackgroundThe current spread of the gene encoding the metallo-ß-lactamase NDM-1 in Enterobacteriaceae is linked to a variety of surrounding genetic structures and plasmid scaffolds.MethodologyThe 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 FindingsPlasmid pGUE-NDM replicating in Escherichia coli confers resistance to many antibiotic molecules including β-lactams, aminoglycosides, trimethoprim, and sulfonamides. It is 87,022 bp in-size and carries the two β-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.SignificanceThis 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.

Antimicrobial Treatment and Containment Measures for an Extremely Drug-Resistant Klebsiella pneumoniae ST101 Isolate Carrying pKPN101-IT, a Novel Fully Sequenced bla KPC-2 Plasmid

“…As recently discussed (29), IncF-like plasmids often provide remarkable virulence and antimicrobial resistance determinants and have a broad host range, covering the entire Enterobacteriaceae family. The newly identified pKPN101-IT plasmid thus has characteristics similar to those of backbones involved in the worldwide dissemination of other resistance determinants, such as bla CTX-M-15 , bla , and, the recently reported bla NDM-1 (3,4).…”

Toxin Kid uncouples DNA replication and cell division to enforce retention of plasmid R1 in Escherichia coli cells

“…Moreover, other observations indicate that our past experiments may have been inappropriate to conclude that Kid does not kill Escherichia coli cells (30,31). Importantly, Kid, Kis, and other elements that we found essential for R1 rescue are conserved in plasmids conferring resistance to extended-spectrum β-lactamases, a worrying threat to human health (1,(6)(7)(8)(9)(10)32). Therapeutic options to fight pathogens carrying these plasmids are limited, and activation of Kid may be perceived as a good antibiotic alternative.…”

“…kis-kid and all other elements required for R1 rescue (i.e., UUACU-positive copB-repA and UUACU-free repA mRNAs) are present in plasmids encoding extended-spectrum β-lactamases, which is a major clinical concern worldwide for which therapeutic alternatives are scarce (1,3,(6)(7)(8)(9)(10), suggesting that the system also operates there. Worth noting, plasmids conferring vancomycin resistance to enterococci also encode fairly conserved Kid and Kis homologs, and their pharmacological activation has also been proposed as a strategy for tailored therapy against these worrisome pathogens (11).…”

“…TA pairs are common in plasmids disseminating antibiotic resistance in bacterial pathogens worldwide (2,(6)(7)(8)(9)(10). The link of these systems to PSK and the exiguous list of alternatives in the pipeline have led some to propose that chemicals activating these TA pairs may constitute a powerful antibiotic approach against these organisms (5,(11)(12)(13).…”

The genetic analysis of Enterobacteriaceae plasmids to provide insights into the acquisition and spread of the blaNDM gene

“…However, it may be misleading to assume that each plasmid of the same replicon type is identical, especially amongst the IncA/C (94,175,177,205) and IncFII plasmids (182,202 The blaNDM genetic context of NDM-producers from Singapore, Japan, Hong Kong, Thailand and Taiwan has been described (74,125,177,203,224). Additionally, NDM-producing…”