Macrolide antibiotic interaction and resistance on the bacterial ribosome

Curr Opin Investig Drugs. 2003 Feb;4(2):140-8.


Our understanding of the fine structure of many antibiotic target sites has reached a new level of enlightenment in the last couple of years due to the advent, by X-ray crystallography, of high-resolution structures of the bacterial ribosome. Many classes of clinically useful antibiotics bind to the ribosome to inhibit bacterial protein synthesis. Macrolide, lincosamide and streptogramin B (MLSB) antibiotics form one of the largest groups, and bind to the same site on the 50S ribosomal subunit. Here, we review the molecular details of the ribosomal MLSB site to put into perspective the main points from a wealth of biochemical and genetic data that have been collected over several decades. The information is now available to understand, at atomic resolution, how macrolide antibiotics interact with their ribosomal target, how the target is altered to confer resistance, and in which directions we need to look if we are to rationally design better drugs to overcome the extant resistance mechanisms.

Publication types

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

MeSH terms

  • Anti-Bacterial Agents / chemistry
  • Anti-Bacterial Agents / pharmacology*
  • Bacteria / drug effects*
  • Bacteria / genetics
  • Bacteria / ultrastructure
  • Drug Resistance, Bacterial / physiology*
  • Macrolides
  • Methylation
  • Models, Molecular
  • Mutation
  • RNA, Ribosomal, 23S / drug effects
  • RNA, Ribosomal, 23S / genetics
  • Ribosomes / drug effects*


  • Anti-Bacterial Agents
  • Macrolides
  • RNA, Ribosomal, 23S