Targeting metallo-β-lactamase enzymes in antibiotic resistance

Future Med Chem. 2013 Jul;5(11):1243-63. doi: 10.4155/fmc.13.55.

Abstract

The β-lactam antibiotics are essential for the treatment of a wide range of human bacterial diseases. However, a class of zinc-dependent hydrolases known as the metallo-β-lactamase (MBL) can confer bacteria with extended spectrum β-lactam resistance. To date, there are no clinically approved MBL inhibitors, making these enzymes a serious threat to human health. In this review, a structural approach is taken to outline some of the more promising MBL inhibitors and shed light on how the resistance conferred by this emerging class of enzymes may be circumvented in the future.

Publication types

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

MeSH terms

  • Aptamers, Nucleotide / chemistry
  • Aptamers, Nucleotide / pharmacology
  • Bacteria / enzymology
  • Carbapenems / chemistry
  • Carbapenems / pharmacology
  • Catalytic Domain
  • Cephalosporins / chemistry
  • Cephalosporins / pharmacology
  • Cyclobutanes / chemistry
  • Cyclobutanes / pharmacology
  • Enzyme Inhibitors / chemistry
  • Enzyme Inhibitors / pharmacology
  • Humans
  • Penicillins / chemistry
  • Penicillins / pharmacology
  • Sulfhydryl Compounds / chemistry
  • Sulfhydryl Compounds / pharmacology
  • beta-Lactam Resistance / drug effects
  • beta-Lactamase Inhibitors*
  • beta-Lactamases / metabolism

Substances

  • Aptamers, Nucleotide
  • Carbapenems
  • Cephalosporins
  • Cyclobutanes
  • Enzyme Inhibitors
  • Penicillins
  • Sulfhydryl Compounds
  • beta-Lactamase Inhibitors
  • beta-Lactamases