Evolution of the serine beta-lactamases: past, present and future

Drug Resist Updat. 2004 Apr;7(2):111-23. doi: 10.1016/j.drup.2004.02.003.


We present a protein structure-based phylogeny of Classes A, C and D of the serine beta-lactamases, and a new, detailed, sequence-based phylogeny of the Class A beta-lactamases. In addition, we discuss the historical evolution of Classes C and D. The evolutionary histories of all three classes indicate that the serine beta-lactamases are ancient enzymes, originating over two billion years ago, and that some have been on plasmids for millions of years. We also discuss the recent, antibiotic-era, evolution of the serine beta-lactamases in response to the clinical use of beta-lactam antibiotics. We also discuss a method that is being used to predict the future evolution of beta-lactamases in response to selection with new drugs.

MeSH terms

  • Anti-Bacterial Agents / chemistry
  • Anti-Bacterial Agents / classification*
  • Anti-Bacterial Agents / therapeutic use
  • Bayes Theorem
  • Evolution, Molecular
  • Phylogeny*
  • beta-Lactamases / classification*
  • beta-Lactamases / genetics
  • beta-Lactamases / physiology
  • beta-Lactamases / therapeutic use


  • Anti-Bacterial Agents
  • beta-lactamase PIT-2
  • beta-Lactamases
  • beta-lactamase TEM-1