Plasmid-Mediated Novel blaNDM-17 Gene Encoding a Carbapenemase with Enhanced Activity in a Sequence Type 48 Escherichia coli Strain

Antimicrob Agents Chemother. 2017 Apr 24;61(5):e02233-16. doi: 10.1128/AAC.02233-16. Print 2017 May.

Abstract

Carbapenem-resistant Enterobacteriaceae (CRE) have spread worldwide, leaving very few treatment options available. New Delhi metallo-beta-lactamase (NDM) is the main carbapenemase mediating CRE resistance and is of increasing concern. NDM-positive Enterobacteriaceae of human origin are frequently identified; however, the emergence of NDM, and particularly novel variants, in bacteria of food animal origin has never been reported. Here, we characterize a novel NDM variant (assigned NDM-17) identified in a β-lactam-resistant sequence type 48 (ST48) Escherichia coli strain that was isolated from a chicken in China. Compared to NDM-1, NDM-17 had three amino acid substitutions (V88L, M154L, and E170K) that confer significantly enhanced carbapenemase activity. Compared to NDM-5, NDM-17 had only one amino acid substitution (E170K) and slightly increased isolate resistance to carbapenem, as indicated by increased MIC values. The gene encoding NDM-17 (blaNDM-17) was located on an IncX3 plasmid, which was readily transferrable to recipient E. coli strain J53 by conjugation, suggesting the possibility of the rapid dissemination of blaNDM-17 Enzyme kinetics showed that NDM-17 could hydrolyze all β-lactams tested, except for aztreonam, and had a significantly higher affinity for all β-lactams tested than did NDM-5. The emergence of this novel NDM variant could pose a threat to public health because of its transferability and enhanced carbapenemase activity.

Keywords: IncX3; NDM-17; ST48; carbapenemase.

MeSH terms

  • Amino Acid Substitution / genetics
  • Animals
  • Anti-Bacterial Agents / pharmacology
  • Bacterial Proteins / genetics*
  • Carbapenem-Resistant Enterobacteriaceae / drug effects
  • Carbapenem-Resistant Enterobacteriaceae / genetics*
  • Chickens
  • China
  • Escherichia coli / drug effects*
  • Escherichia coli / genetics*
  • Escherichia coli / isolation & purification
  • Escherichia coli Proteins / genetics*
  • Gene Transfer, Horizontal / genetics
  • Microbial Sensitivity Tests
  • Plasmids / genetics*
  • beta-Lactamases / genetics*
  • beta-Lactams / pharmacology

Substances

  • Anti-Bacterial Agents
  • Bacterial Proteins
  • Escherichia coli Proteins
  • beta-Lactams
  • beta-Lactamases
  • beta-lactamase NDM-17, E coli
  • carbapenemase