Related Experiment Video

Updated: Apr 22, 2026

Measurement of Specific Mycobacterial Mistranslation Rates with Gain-of-function Reporter Systems
06:18

Measurement of Specific Mycobacterial Mistranslation Rates with Gain-of-function Reporter Systems

Published on: April 26, 2019

6.5K

Sequence selectivity of macrolide-induced translational attenuation

Amber R Davis1, David W Gohara1, Mee-Ngan F Yap2

  • 1Edward A. Doisy Department of Biochemistry and Molecular Biology, Saint Louis University School of Medicine, St. Louis, MO 63104.

Proceedings of the National Academy of Sciences of the United States of America
|October 15, 2014
PubMed

Insights

Macrolide antibiotics like azithromycin do not stall bacterial protein synthesis at a fixed point. Instead, they cause specific ribosome stalling at diverse sites rich in proline and charged residues.

Area of Science:

  • Microbiology
  • Molecular Biology
  • Antibiotic Resistance

Background:

  • The "plug-in-the-bottle" model posits macrolide antibiotics halt bacterial translation universally after 6-8 amino acids.
  • This model suggests indiscriminate inhibition within the ribosome tunnel.

Purpose of the Study:

  • To investigate the precise mechanism of macrolide-induced translation inhibition in Staphylococcus aureus.
  • To challenge the prevailing "plug-in-the-bottle" model of macrolide action.

Main Methods:

  • Genome-wide analysis of translation.
  • Treatment of Staphylococcus aureus with azithromycin.
  • Identification and characterization of ribosome stalling sites.

Main Results:

  • Macrolides do not induce preferential ribosome stalling near the 5' end of mRNAs.
  • Specific stalling sites are scattered throughout coding regions, enriched in prolines and charged residues.
  • Structurally similar macrolides exhibit varying stalling efficiencies.

Conclusions:

  • Ribosome stalling by macrolides is not indiscriminate but occurs at specific motifs.
  • Stalling efficiency depends on arrest-inducing residues and the presence of the macrolide inducer.
  • The "plug-in-the-bottle" model is an oversimplification of macrolide antibiotic action.
Keywords:
Staphylococcus aureusantibioticribosome stalling

More Related Videos

Isolation of Translating Ribosomes Containing Peptidyl-tRNAs for Functional and Structural Analyses11:19

Isolation of Translating Ribosomes Containing Peptidyl-tRNAs for Functional and Structural Analyses

Published on: February 25, 2011

20.5K
Assessment of Selective mRNA Translation in Mammalian Cells by Polysome Profiling10:00

Assessment of Selective mRNA Translation in Mammalian Cells by Polysome Profiling

Published on: October 28, 2014

27.9K

Related Concept Videos

Inhibitors of Bacterial Protein Synthesis01:25

Inhibitors of Bacterial Protein Synthesis

Aminoglycosides constitute a highly potent class of bactericidal antibiotics that exert their antimicrobial effects by targeting the bacterial ribosome, specifically disrupting protein synthesis. These polycationic molecules consist of amino-modified sugars linked via glycosidic bonds to an aminocyclitol core such as 2-deoxystreptamine or streptamine. Their strong positive charges facilitate tight binding to the negatively charged phosphate backbone of ribosomal RNA (rRNA), primarily at the 16S...
93
Improving Translational Accuracy02:07

Improving Translational Accuracy

Base complementarity between the three base pairs of mRNA codon and the tRNA anticodon is not a failsafe mechanism. Inaccuracies can range from a single mismatch to no correct base pairing at all. The free energy difference between the correct and nearly correct base pairs can be as small as 3 kcal/ mol. With complementarity being the only proofreading step, the estimated error frequency would be one wrong amino acid in every 100 amino acids incorporated. However, error frequencies observed in...
11.5K
Transcription Attenuation in Prokaryotes02:42

Transcription Attenuation in Prokaryotes

Transcriptional attenuation occurs when RNA transcription is prematurely terminated due to the formation of a terminator mRNA hairpin structure.  Bacteria use these hairpins to regulate the transcription process and control the synthesis of several amino acids including histidine, lysine, threonine, and phenylalanine. Transcription attenuation takes place in the non-coding regions of mRNA.
There are several different mechanisms used to attenuate transcription. In ribosome mediated...
14.5K
Translational Regulation01:29

Translational Regulation

Translational regulation in prokaryotes ensures efficient protein synthesis by controlling ribosome access to mRNA. This regulation is mediated by secondary RNA structures, including translational riboswitches, RNA thermometers, and small RNAs (sRNAs), which respond to intracellular and environmental signals to modulate gene expression.Translational RiboswitchesRiboswitches in the leader region of mRNAs can regulate translation by altering the accessibility of the Shine-Dalgarno (SD) sequence,...
861
Leaky Scanning02:28

Leaky Scanning

During most eukaryotic translation processes, the small 40S ribosome subunit scans an mRNA from its 5' end until it encounters the first start AUG codon. The large 60S ribosomal subunit then joins the smaller one to initiate protein synthesis. The location of the translation initiation is largely determined by the nucleotides near the start codon as there may be multiple translation initiation sites present on the mRNA.  Marilyn Kozak discovered that the sequence RCCAUGG (where R...
4.5K
Mechanism of Antibiotic Resistance in MRSA01:25

Mechanism of Antibiotic Resistance in MRSA

Antibiotic resistance in bacteria arises when microorganisms evolve the ability to withstand drugs designed to kill them or inhibit their growth, rendering once-effective treatments useless. This phenomenon, driven by genetic change and selection under antibiotic exposure, poses a profound threat to modern medicine. Mechanisms include drug-inactivating enzymes (e.g., β-lactamases), efflux pumps that eject antibiotics, mutations altering antibiotic targets, decreased drug uptake, and...
180