Ribosome-Targeting Antibiotics: Modes of Action, Mechanisms of Resistance, and Implications for Drug Design

Annu Rev Biochem. 2018 Jun 20;87:451-478. doi: 10.1146/annurev-biochem-062917-011942. Epub 2018 Mar 23.


Genetic information is translated into proteins by the ribosome. Structural studies of the ribosome and of its complexes with factors and inhibitors have provided invaluable information on the mechanism of protein synthesis. Ribosome inhibitors are among the most successful antimicrobial drugs and constitute more than half of all medicines used to treat infections. However, bacterial infections are becoming increasingly difficult to treat because the microbes have developed resistance to the most effective antibiotics, creating a major public health care threat. This has spurred a renewed interest in structure-function studies of protein synthesis inhibitors, and in few cases, compounds have been developed into potent therapeutic agents against drug-resistant pathogens. In this review, we describe the modes of action of many ribosome-targeting antibiotics, highlight the major resistance mechanisms developed by pathogenic bacteria, and discuss recent advances in structure-assisted design of new molecules.

Keywords: antibiotic resistance; antibiotics; drug design; mechanisms of inhibition; protein synthesis; ribosome.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Anti-Bacterial Agents / chemistry
  • Anti-Bacterial Agents / pharmacology*
  • Antimicrobial Cationic Peptides / chemistry
  • Antimicrobial Cationic Peptides / pharmacology
  • Binding Sites
  • Drug Design
  • Drug Resistance, Microbial
  • Humans
  • Models, Biological
  • Models, Molecular
  • Protein Biosynthesis / drug effects
  • Protein Synthesis Inhibitors / chemistry
  • Protein Synthesis Inhibitors / pharmacology
  • Ribosomes / chemistry
  • Ribosomes / drug effects*
  • Ribosomes / metabolism
  • Structure-Activity Relationship


  • Anti-Bacterial Agents
  • Antimicrobial Cationic Peptides
  • Protein Synthesis Inhibitors