The bacterial ribosome as a target for antibiotics

  title={The bacterial ribosome as a target for antibiotics},
  author={Jacob Poehlsgaard and Stephen Douthwaite},
  journal={Nature Reviews Microbiology},
Many clinically useful antibiotics exert their antimicrobial effects by blocking protein synthesis on the bacterial ribosome. The structure of the ribosome has recently been determined by X-ray crystallography, revealing the molecular details of the antibiotic-binding sites. The crystal data explain many earlier biochemical and genetic observations, including how drugs exercise their inhibitory effects, how some drugs in combination enhance or impede each other's binding, and how alterations to… 

Ribosome-targeting antibiotics and mechanisms of bacterial resistance

The recent structural insights into the mechanism of action of ribosome-targeting antibiotics and the molecular mechanisms of bacterial resistance are discussed, in addition to the approaches that are being pursued for the production of improved drugs that inhibit bacterial protein synthesis.

Antibiotics that target protein synthesis

The major classes of antibiotics that target the bacterial ribosome are discussed and classified according to their respective target.

Elements of ribosomal drug resistance and specificity.

The ribosome as a drug target.

  • E. Böttger
  • Biology, Chemistry
    Trends in biotechnology
  • 2006

Using sequence-specific oligonucleotides to inhibit bacterial rRNA.

Nonconventional approaches to screening for ribosome inhibition and function of particular rRNA regions are described, including inhibitors against rRNA that may be designed according to nucleotide sequence and higher order structure.

The chemistry of peptidyltransferase center-targeted antibiotics: enzymatic resistance and approaches to countering resistance.

Recent advances in the elucidation of chemical mechanisms underlying resistance and driving the development of new antibiotics are discussed.

Structural basis for hygromycin B inhibition of protein biosynthesis.

The structure of the intact Escherichia coli 70S ribosome in complex with hygromycin B is described and structural and biochemical results help to explain the unique mode of translation inhibition by hygroitcin B.

Allosteric control of the ribosome by small-molecule antibiotics

Findings reveal the functional importance of reversible intersubunit rotation to the translation mechanism and shed new light on the allosteric control of ribosome functions by small-molecule antibiotics.

4′-O-substitutions determine selectivity of aminoglycoside antibiotics

The data indicate that 4′-O-substituted aminoglycosides possess increased selectivity towards bacterial ribosomes and little activity for any of the human drug-binding pockets.

Structures of the Escherichia coli ribosome with antibiotics bound near the peptidyl transferase center explain spectra of drug action

X-ray crystal structures of the Escherichia coli ribosome in complexes with clinically important antibiotics of four major classes are reported, arguing that the identity of nucleotides 752, 2609, and 2055 of 23S ribosomal RNA explain in part the spectrum and selectivity of antibiotic action.



Drugs targeting the ribosome.

  • T. Hermann
  • Biology, Chemistry
    Current opinion in structural biology
  • 2005

Ribosomal Antibiotics

  • A. Mankin
  • Biology, Chemistry
    Molecular Biology
  • 2004
In spite of decades of research, our understanding of the principles of antibiotic binding to the ribosome and the mechanisms of drug action remains only fragmentary. Recent progress in biochemical

Bacterial ribosomal subunit assembly is an antibiotic target.

  • W. S. Champney
  • Biology, Chemistry
    Current topics in medicinal chemistry
  • 2003
This review will describe features of this new target including the types of compounds which affect particle assembly and differences in the process in different microorganisms.

Structural basis for the interaction of antibiotics with the peptidyl transferase centre in eubacteria

The details of antibiotic interactions with the components of their binding sites are reported and the importance of putative Mg+2 ions for the binding of some drugs is shown to facilitate rational drug design.

The macrolide binding site on the bacterial ribosome.

In the on-going battle against resistance pathogens continual improvement of drugs will be necessary, and more efficient means of drug development are required, an indication of how rational drug design might be feasible is offered by the recent crystallographic structures of the bacterial ribosome.

Structural origins of gentamicin antibiotic action

The structure of gentamicin leads to a general model for specific ribosome recognition by aminoglycoside antibiotics and a possible mechanism for translational inhibition and miscoding, and provides a structural rationale for chemical synthesis of novel am inoglycosides.

Interaction of antibiotics with functional sites in 16S ribosomal RNA

Chemical footprinting shows that several classes of antibiotics protect concise sets of highly conserved nucleotides in 16S ribosomal RNA when bound to ribosomes, having strong implications for the mechanism of action of these antibiotics and for the assignment of functions to specific structural features of 16S rRNA.

Throwing a spanner in the works: antibiotics and the translation apparatus

The current understanding as to how antibiotics disrupt this process is reviewed here, with particular emphasis on the prokaryotic elongation cycle and those drugs that interact with ribosomal RNAs.

Binding Site of Macrolide Antibiotics on the Ribosome: New Resistance Mutation Identifies a Specific Interaction of Ketolides with rRNA

The location of the macrolide binding site in the nascent peptide exit tunnel at some distance from the peptidyl transferase center agrees with the proposed model of macrolides inhibitory action and explains the dominant nature of macolide resistance mutations.

Interaction of Avilamycin with Ribosomes and Resistance Caused by Mutations in 23S rRNA

It is inferred that avilamycin interacts with the Ribosomes at the ribosomal A-site interfering with initiation factor IF2 and tRNA binding in a manner similar to evernimicin.