A Decrease in Transcription Capacity Limits Growth Rate upon Translation Inhibition

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 de...

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Autores principales:	Qing Zhang, Elisa Brambilla, Rui Li, Hualin Shi, Marco Cosentino Lagomarsino, Bianca Sclavi
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2020
Materias:	antibiotic transcription translation Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/4196c582611c4153b8aefeb1fc88130a
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spelling	oai:doaj.org-article:4196c582611c4153b8aefeb1fc88130a2021-12-02T19:47:33ZA Decrease in Transcription Capacity Limits Growth Rate upon Translation Inhibition10.1128/mSystems.00575-202379-5077https://doaj.org/article/4196c582611c4153b8aefeb1fc88130a2020-10-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mSystems.00575-20https://doaj.org/toc/2379-5077ABSTRACT 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.Qing ZhangElisa BrambillaRui LiHualin ShiMarco Cosentino LagomarsinoBianca SclaviAmerican Society for MicrobiologyarticleantibiotictranscriptiontranslationMicrobiologyQR1-502ENmSystems, Vol 5, Iss 5 (2020)
institution	DOAJ
collection	DOAJ
language	EN
topic	antibiotic transcription translation Microbiology QR1-502
spellingShingle	antibiotic transcription translation Microbiology QR1-502 Qing Zhang Elisa Brambilla Rui Li Hualin Shi Marco Cosentino Lagomarsino Bianca Sclavi A Decrease in Transcription Capacity Limits Growth Rate upon Translation Inhibition
description	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.
format	article
author	Qing Zhang Elisa Brambilla Rui Li Hualin Shi Marco Cosentino Lagomarsino Bianca Sclavi
author_facet	Qing Zhang Elisa Brambilla Rui Li Hualin Shi Marco Cosentino Lagomarsino Bianca Sclavi
author_sort	Qing Zhang
title	A Decrease in Transcription Capacity Limits Growth Rate upon Translation Inhibition
title_short	A Decrease in Transcription Capacity Limits Growth Rate upon Translation Inhibition
title_full	A Decrease in Transcription Capacity Limits Growth Rate upon Translation Inhibition
title_fullStr	A Decrease in Transcription Capacity Limits Growth Rate upon Translation Inhibition
title_full_unstemmed	A Decrease in Transcription Capacity Limits Growth Rate upon Translation Inhibition
title_sort	decrease in transcription capacity limits growth rate upon translation inhibition
publisher	American Society for Microbiology
publishDate	2020
url	https://doaj.org/article/4196c582611c4153b8aefeb1fc88130a
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A Decrease in Transcription Capacity Limits Growth Rate upon Translation Inhibition

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