Ribosome-Targeting Antibiotics

Modes of Action, Mechanisms of Resistance, and Implications for Drug Design

Jinzhong Lin, Dejian Zhou, Thomas A. Steitz, Yury S. Polikanov, Matthieu Gagnon

Research output: Contribution to journalReview article

17 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)451-478
Number of pages28
JournalAnnual Review of Biochemistry
Volume87
DOIs
StatePublished - Jun 20 2018

Fingerprint

Drug Design
Ribosomes
Anti-Bacterial Agents
Protein Synthesis Inhibitors
Public health
Pathogens
Health care
Pharmaceutical Preparations
Medicine
Bacteria
Proteins
Molecules
Bacterial Infections
Public Health
Delivery of Health Care
Infection
Therapeutics

Keywords

  • antibiotic resistance
  • antibiotics
  • drug design
  • mechanisms of inhibition
  • protein synthesis
  • ribosome

ASJC Scopus subject areas

  • Biochemistry

Cite this

Ribosome-Targeting Antibiotics : Modes of Action, Mechanisms of Resistance, and Implications for Drug Design. / Lin, Jinzhong; Zhou, Dejian; Steitz, Thomas A.; Polikanov, Yury S.; Gagnon, Matthieu.

In: Annual Review of Biochemistry, Vol. 87, 20.06.2018, p. 451-478.

Research output: Contribution to journalReview article

Lin, Jinzhong ; Zhou, Dejian ; Steitz, Thomas A. ; Polikanov, Yury S. ; Gagnon, Matthieu. / Ribosome-Targeting Antibiotics : Modes of Action, Mechanisms of Resistance, and Implications for Drug Design. In: Annual Review of Biochemistry. 2018 ; Vol. 87. pp. 451-478.
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