ArticleProceedings of the National Academy of Sciences of the United States of America2014
Correcting direct effects of ethanol on translation and transcription machinery confers ethanol tolerance in bacteria.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 80 papers.
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Who cites it
80 citing papers in PubMed, 163 citations in OpenAlex.
- Impact of alcohol on gut microbial metabolism and the gut-liver-brain axis.Alcohol (Fayetteville, N.Y.) · 2026Review
- UGA4 and YBR062C Regulate Oxidative Stress Tolerance Under Heavy Metal Toxicity.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2026Article
- When Disinfection Fails: Biocide Tolerance as a Driver ofAntibiotics (Basel, Switzerland) · 2026Review
- Orthogonal chemical genomics approaches reveal genomic targets for increasing anaerobic chemical tolerance inmSystems · 2026Article
- Engineering Escherichia coli to produce medium chain oleochemicals from C2 substrates.Journal of industrial microbiology & biotechnology · 2026Article
- Reprogramming the EnvZ-OmpR two-component system confers ethanol tolerance in Escherichia coli by stabilizing the outer membrane and altering ferric homeostasis.PLoS genetics · 2025Article
- Rho-dependent transcription termination: mechanisms and roles in bacterial fitness and adaptation to environmental changes.RNA (New York, N.Y.) · 2025Review
- Nucleotide-induced hyper-oligomerization inactivates transcription termination factor ρ.Nature communications · 2025Article
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- Structure and metabolic function of spatiotemporal pit mud microbiome.Environmental microbiome · 2025Article
- Evolution of pH-sensitive transcription termination inProceedings of the National Academy of Sciences of the United States of America · 2024Article
- Evolution of pH-sensitive transcription termination during adaptation to repeated long-term starvation.bioRxiv : the preprint server for biology · 2024Article
- In Vitro Transcription Assay to Quantify Effects of H-NS Filaments on RNA Chain Elongation by RNA Polymerase.Methods in molecular biology (Clifton, N.J.) · 2024Article
- Advance of tolerance engineering on microbes for industrial production.Synthetic and systems biotechnology · 2023Review
- Ethanol- and PARP-Mediated Regulation of Ribosome-Associated Long Non-Coding RNA (lncRNA) in Pyramidal Neurons.Non-coding RNA · 2023Article
- Ethanol tolerance in engineered strains of Clostridium thermocellum.Biotechnology for biofuels and bioproducts · 2023Article
- Single-nucleus resolution mapping of the adult C. elegans and its application to elucidate inter- and trans-generational response to alcohol.Cell reports · 2023Article
- Design of a stable ethanologenic bacterial strain without heterologous plasmids and antibiotic resistance genes for efficient ethanol production from concentrated dairy waste.Biotechnology for biofuels and bioproducts · 2023Article
- Termination factor Rho mediates transcriptional reprogramming of Bacillus subtilis stationary phase.PLoS genetics · 2023Article
- Production of (2Synthetic and systems biotechnology · 2022Article
20 more citing papers are in PubMed but not listed here.
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Authors and funding
13 authors at 2 institutions in 2 countries.
Funding
Abstract
The molecular mechanisms of ethanol toxicity and tolerance in bacteria, although important for biotechnology and bioenergy applications, remain incompletely understood. Genetic studies have identified potential cellular targets for ethanol and have revealed multiple mechanisms of tolerance, but it remains difficult to separate the direct and indirect effects of ethanol. We used adaptive evolution to generate spontaneous ethanol-tolerant strains of Escherichia coli, and then characterized mechanisms of toxicity and resistance using genome-scale DNAseq, RNAseq, and ribosome profiling coupled with specific assays of ribosome and RNA polymerase function. Evolved alleles of metJ, rho, and rpsQ recapitulated most of the observed ethanol tolerance, implicating translation and transcription as key processes affected by ethanol. Ethanol induced miscoding errors during protein synthesis, from which the evolved rpsQ allele protected cells by increasing ribosome accuracy. Ribosome profiling and RNAseq analyses established that ethanol negatively affects transcriptional and translational processivity. Ethanol-stressed cells exhibited ribosomal stalling at internal AUG codons, which may be ameliorated by the adaptive inactivation of the MetJ repressor of methionine biosynthesis genes. Ethanol also caused aberrant intragenic transcription termination for mRNAs with low ribosome density, which was reduced in a strain with the adaptive rho mutation. Furthermore, ethanol inhibited transcript elongation by RNA polymerase in vitro. We propose that ethanol-induced inhibition and uncoupling of mRNA and protein synthesis through direct effects on ribosomes and RNA polymerase conformations are major contributors to ethanol toxicity in E. coli, and that adaptive mutations in metJ, rho, and rpsQ help protect these central dogma processes in the presence of ethanol.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.