An unexpected similarity between antibiotic-resistant NDM-1 and beta-lactamase II from Erythrobacter litoralis

Protein Cell. 2011 Mar;2(3):250-8. doi: 10.1007/s13238-011-1027-0. Epub 2011 Apr 6.

Abstract

NDM-1 (New Delhi metallo-beta-lactamase) gene encodes a metallo-beta-lactamase (MBL) with high carbapenemase activity, which makes the host bacterial strain easily dispatch the last-resort antibiotics known as carbapenems and cause global concern. Here we present the bioinformatics data showing an unexpected similarity between NDM-1 and beta-lactamase II from Erythrobacter litoralis, a marine microbial isolate. We have further expressed these two mature proteins in E. coli cells, both of which present as a monomer with a molecular mass of 25 kDa. Antimicrobial susceptibility assay reveals that they share similar substrate specificities and are sensitive to aztreonam and tigecycline. The conformational change accompanied with the zinc binding visualized by nuclear magnetic resonance, Zn(2+)-bound NDM-1, adopts at least some stable tertiary structure in contrast to the metal-free protein. Our work implies a close evolutionary relationship between antibiotic resistance genes in environmental reservoir and in the clinic, challenging the antimicrobial resistance monitoring.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Anti-Bacterial Agents / pharmacology*
  • Aztreonam / pharmacology
  • Cephalosporinase / chemistry
  • Cephalosporinase / genetics*
  • Cephalosporinase / metabolism
  • Computational Biology / methods*
  • Drug Resistance, Bacterial / genetics*
  • Enzyme Stability / drug effects
  • Evolution, Molecular
  • Minocycline / analogs & derivatives
  • Minocycline / pharmacology
  • Molecular Sequence Data
  • Phylogeny
  • Protein Structure, Tertiary / drug effects
  • Sequence Homology, Nucleic Acid
  • Sphingomonadaceae / drug effects
  • Sphingomonadaceae / enzymology*
  • Sphingomonadaceae / genetics*
  • Tigecycline
  • Zinc / pharmacology
  • beta-Lactamases / chemistry
  • beta-Lactamases / genetics*
  • beta-Lactamases / metabolism

Substances

  • Anti-Bacterial Agents
  • Tigecycline
  • Cephalosporinase
  • beta-Lactamases
  • beta-lactamase NDM-1
  • Minocycline
  • Aztreonam
  • Zinc