Plasmid-mediated novel blaNDM-17 gene encoding a carbapenemase with enhanced activity in a sequence type 48 Escherichia coli Strain

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.