Biochemical characteristics of New Delhi metallo-β-lactamase-1 show unexpected difference to other MBLs

PLoS One. 2013 Apr 12;8(4):e61914. doi: 10.1371/journal.pone.0061914. Print 2013.

Abstract

New Delhi metallo-β-lactamase (NDM-1) is a new metallo-β-lactamase (MBL) that has recently emerged as a global threat because it confers bacteria with resistance to almost all clinically used β-lactam antibiotics. To determine the molecular basis of this threat, NDM-1 was purified from Escherichia coli TransB (DE3) carrying cloned blaNDM-1 gene by an anion-exchange chromatography step followed by a gel permeation chromatography step. The purified enzyme was stable even in extremely alkaline buffer (pH 11) and reached its highest activity at a low temperature (15°C), which was different from other MBLs. The 50% inhibition concentration of EDTA against NDM-1 was 412 nM, which showed that NDM-1 was more susceptible to EDTA than other MBLs. The effects of zinc on NDM-1 differed between cephem and carbapenem complexes, but inhibition at high Zn(2+) concentration was observed for all of tested β-lactam compounds.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Biocatalysis / drug effects
  • Edetic Acid / pharmacology
  • Electrophoresis, Polyacrylamide Gel
  • Enzyme Stability / drug effects
  • Escherichia coli / drug effects
  • Escherichia coli / enzymology*
  • Humans
  • Hydrogen-Ion Concentration / drug effects
  • Hydrolysis / drug effects
  • Inhibitory Concentration 50
  • Kinetics
  • Substrate Specificity / drug effects
  • Temperature
  • Zinc / pharmacology
  • beta-Lactamases / isolation & purification
  • beta-Lactamases / metabolism*
  • beta-Lactams / pharmacology

Substances

  • beta-Lactams
  • Edetic Acid
  • beta-Lactamases
  • beta-lactamase NDM-1
  • Zinc

Grants and funding

This work is supported by National Natural Science Foundation of China (No. 81072677). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.