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A Decrease in Transcription Capacity Limits Growth Rate upon Translation Inhibition.

Qing Zhang1, Elisa Brambilla1, Rui Li2

  • 1LBPA, UMR 8113 CNRS, ENS Paris-Saclay, Cachan, France.

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Summary
This summary is machine-generated.

Sublethal antibiotic concentrations reduce bacterial growth by depleting free RNA polymerase (RNAP), impacting long gene translation more than short ribosomal genes.

Keywords:
antibiotictranscriptiontranslation

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Area of Science:

  • Bacteriology
  • Molecular Biology
  • Genetics

Background:

  • Sublethal antibiotic concentrations inhibit bacterial ribosomes, decreasing growth rate despite increased ribosome content.
  • This inhibition increases expression from ribosomal promoters, potentially depleting RNA polymerase (RNAP) for other genes.

Purpose of the Study:

  • To quantify the reduction in free RNAP concentration caused by sublethal antibiotic concentrations.
  • To investigate the impact of RNAP depletion on the transcription of both ribosomal and nonribosomal genes.
  • To explore the mRNA length-dependent effects on protein translation under ribosome inhibition.

Main Methods:

  • Utilized constitutive promoters with varying RNAP affinities to measure free RNAP concentration changes.
  • Employed different reporter genes to assess mRNA length-dependent translation efficiency.
  • Analyzed gene lengths for RNAP subunits and ribosomal proteins in *Escherichia coli*.

Main Results:

  • Demonstrated a significant decrease in free RNAP available for transcription of both ribosomal and nonribosomal genes.
  • Observed that longer genes, like those for RNAP subunits, are more affected by decreased ribosome processivity.
  • Showed that shorter ribosomal genes are less impacted, consistent with their increased expression under these conditions.

Conclusions:

  • Antibiotic-induced ribosome inhibition reduces bacterial growth by limiting RNAP availability for transcription.
  • The differential impact on long vs. short genes explains the observed shift in gene expression favoring ribosomal genes.
  • This mechanism contributes to bacterial adaptation and potential antibiotic resistance development.