Detection of NDM-7 in Germany, a New Variant of the New Delhi metallo-β-lactamase With Increased Carbapenemase Activity

J Antimicrob Chemother. 2013 Aug;68(8):1737-40. doi: 10.1093/jac/dkt088. Epub 2013 Apr 3.

Abstract

Objectives: This study characterized a new variant of the New Delhi metallo-β-lactamase (NDM).

Methods: A multidrug-resistant Escherichia coli isolate was recovered from the wounds, throat and rectum of a Yemeni patient who presented at the Frankfurt University Hospital in Germany. The presence of β-lactamase genes was analysed by PCR and sequencing. The isolate was further characterized by susceptibility testing, conjugation and transformation assays and plasmid analysis.

Results: The E. coli isolate was resistant to all β-lactams including carbapenems. By PCR analysis, the β-lactamase genes blaCMY-2, blaCTX-M-15, blaTEM-1 and blaNDM were identified. Sequencing revealed a blaNDM gene that differed from blaNDM-1 by two point mutations at positions 388 (G→A) and 460 (A→C) corresponding to amino acid substitutions Asp130Asn and Met154Leu, respectively. This NDM variant was identified as NDM-7. The blaNDM-7 gene was located on a self-transferable IncX3 plasmid of 60 kb. E. coli TOP10 transformants harbouring NDM-7 showed higher MICs of β-lactams including carbapenems compared with transformants harbouring NDM-1. Multilocus sequence typing analysis revealed that the E. coli isolate belonged to a novel sequence type (ST599).

Conclusions: This study identified a novel NDM variant in E. coli, NDM-7, possessing a high ability to hydrolyse β-lactam antibiotics. Given the diversity of NDM variants located on self-transferable plasmids found in different Gram-negative species and isolated in different countries, the blaNDM gene will most likely efficiently disseminate worldwide.

Keywords: Enterobacteriaceae; IncX3; NDM-1; antibiotic resistance; carbapenems.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Bacterial Proteins / genetics*
  • Bacterial Proteins / metabolism*
  • Conjugation, Genetic
  • DNA, Bacterial / genetics
  • Escherichia coli / drug effects*
  • Escherichia coli / enzymology*
  • Escherichia coli / genetics
  • Escherichia coli / isolation & purification
  • Escherichia coli Infections / microbiology*
  • Genotype
  • Germany
  • Humans
  • Microbial Sensitivity Tests
  • Multilocus Sequence Typing
  • Pharynx / microbiology
  • Plasmids
  • Polymerase Chain Reaction
  • Rectum / microbiology
  • Transformation, Bacterial
  • Wounds and Injuries / microbiology
  • beta-Lactamases / genetics*
  • beta-Lactamases / metabolism*

Substances

  • Bacterial Proteins
  • DNA, Bacterial
  • beta-Lactamases
  • carbapenemase