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

Authors
  • Zhang, Qing1
  • Brambilla, Elisa1
  • Li, Rui2
  • Shi, Hualin2, 3
  • Cosentino Lagomarsino, Marco4
  • Sclavi, Bianca5
  • 1 LBPA, UMR 8113 CNRS, ENS Paris-Saclay, Cachan, France. , (France)
  • 2 CAS Key Laboratory of Theoretical Physics, Institute of Theoretical Physics, Chinese Academy of Sciences, Beijing, China. , (China)
  • 3 School of Physical Sciences, University of Chinese Academy of Sciences, Beijing, China. , (China)
  • 4 LCQB, UMR 7238 CNRS, Sorbonne Université, Paris, France. , (France)
  • 5 LBPA, UMR 8113 CNRS, ENS Paris-Saclay, Cachan, France [email protected] , (France)
Type
Published Article
Journal
mSystems
Publication Date
Sep 08, 2020
Volume
5
Issue
5
Identifiers
DOI: 10.1128/mSystems.00575-20
PMID: 32900870
Source
Medline
Keywords
Language
English
License
Unknown

Abstract

In bacterial cells, inhibition of ribosomes by sublethal concentrations of antibiotics leads to a decrease in the growth rate despite an increase in ribosome content. The limitation of ribosomal activity results in an increase in the level of expression from ribosomal promoters; this can deplete the pool of RNA polymerase (RNAP) that is available for the expression of nonribosomal genes. However, the magnitude of this effect remains to be quantified. Here, we use the change in the activity of constitutive promoters with different affinities for RNAP to quantify the change in the concentration of free RNAP. The data are consistent with a significant decrease in the amount of RNAP available for transcription of both ribosomal and nonribosomal genes. Results obtained with different reporter genes reveal an mRNA length dependence on the amount of full-length translated protein, consistent with the decrease in ribosome processivity affecting more strongly the translation of longer genes. The genes coding for the β and β' subunits of RNAP are among the longest genes in the Escherichia coli genome, while the genes coding for ribosomal proteins are among the shortest genes. This can explain the observed decrease in transcription capacity that favors the expression of genes whose promoters have a high affinity for RNAP, such as ribosomal promoters.IMPORTANCE Exposure of bacteria to sublethal concentrations of antibiotics can lead to bacterial adaptation and survival at higher doses of inhibitors, which in turn can lead to the emergence of antibiotic resistance. The presence of sublethal concentrations of antibiotics targeting translation results in an increase in the amount of ribosomes per cell but nonetheless a decrease in the cells' growth rate. In this work, we have found that inhibition of ribosome activity can result in a decrease in the amount of free RNA polymerase available for transcription, thus limiting the protein expression rate via a different pathway than what was expected. This result can be explained by our observation that long genes, such as those coding for RNA polymerase subunits, have a higher probability of premature translation termination in the presence of ribosome inhibitors, while expression of short ribosomal genes is affected less, consistent with their increased concentration. Copyright © 2020 Zhang et al.

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