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Comparative Analysis of Transcriptomic Response of Escherichia coli K-12 MG1655 to Nine Representative Classes of Antibiotics

The use of antibiotics leads to strong stresses to bacteria, leading to profound impact on cellular physiology. Elucidating how bacteria respond to antibiotic stresses not only helps us to decipher bacteria’s strategies to resistant antibiotics but also assists in proposing targets for antibiotic de...

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Autores principales: Bie, Luyao, Zhang, Mengge, Wang, Juan, Fang, Meng, Li, Ling, Xu, Hai, Wang, Mingyu
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Society for Microbiology 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10100721/
https://www.ncbi.nlm.nih.gov/pubmed/36853057
http://dx.doi.org/10.1128/spectrum.00317-23
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author Bie, Luyao
Zhang, Mengge
Wang, Juan
Fang, Meng
Li, Ling
Xu, Hai
Wang, Mingyu
author_facet Bie, Luyao
Zhang, Mengge
Wang, Juan
Fang, Meng
Li, Ling
Xu, Hai
Wang, Mingyu
author_sort Bie, Luyao
collection PubMed
description The use of antibiotics leads to strong stresses to bacteria, leading to profound impact on cellular physiology. Elucidating how bacteria respond to antibiotic stresses not only helps us to decipher bacteria’s strategies to resistant antibiotics but also assists in proposing targets for antibiotic development. In this work, a comprehensive comparative transcriptomic analysis on how Escherichia coli responds to nine representative classes of antibiotics (tetracycline, mitomycin C, imipenem, ceftazidime, kanamycin, ciprofloxacin, polymyxin E, erythromycin, and chloramphenicol) was performed, aimed at determining and comparing the responses of this model organism to antibiotics at the transcriptional level. On average, 39.71% of genes were differentially regulated by antibiotics at concentrations that inhibit 50% growth. Kanamycin leads to the strongest transcriptomic response (76.4% of genes regulated), whereas polymyxin E led to minimal transcriptomic response (4.7% of genes regulated). Further GO, KEGG, and EcoCyc enrichment analysis found significant transcriptomic changes in carbon metabolism, amino acid metabolism, nutrient assimilation, transport, stress response, nucleotide metabolism, protein biosynthesis, cell wall biosynthesis, energy conservation, mobility, and cell-environmental communications. Analysis of coregulated genes led to the finding of significant reduction of sulfur metabolism by all antibiotics, and analysis of transcription factor-coding genes suggested clustered regulatory patterns implying coregulation. In-depth analysis of regulated pathways revealed shared and unique strategies of E. coli resisting antibiotics, leading to the proposal of four different strategies (the pessimistic, the ignorant, the defensive, and the invasive). In conclusion, this work provides a comprehensive analysis of E. coli’s transcriptomic response to antibiotics, which paves the road for further physiological investigation. IMPORTANCE Antibiotics are among the most important inventions in the history of humankind. They are the ultimate reason why bacterial infections are no longer the number one threat to people’s lives. However, the wide application of antibiotics in the last half a century has led to aggravating antibiotic resistance, weakening the efficacy of antibiotics. To better comprehend the ways bacteria deal with antibiotics that may eventually turn into resistance mechanisms, and to identify good targets for potential antibiotics, knowledge on how bacteria regulate their physiology in response to different classes of antibiotics is needed. This work aimed to fill this knowledge gap by identifying changes of bacterial functions at the transcription level and suggesting strategies of bacteria to resist antibiotics.
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spelling pubmed-101007212023-04-14 Comparative Analysis of Transcriptomic Response of Escherichia coli K-12 MG1655 to Nine Representative Classes of Antibiotics Bie, Luyao Zhang, Mengge Wang, Juan Fang, Meng Li, Ling Xu, Hai Wang, Mingyu Microbiol Spectr Research Article The use of antibiotics leads to strong stresses to bacteria, leading to profound impact on cellular physiology. Elucidating how bacteria respond to antibiotic stresses not only helps us to decipher bacteria’s strategies to resistant antibiotics but also assists in proposing targets for antibiotic development. In this work, a comprehensive comparative transcriptomic analysis on how Escherichia coli responds to nine representative classes of antibiotics (tetracycline, mitomycin C, imipenem, ceftazidime, kanamycin, ciprofloxacin, polymyxin E, erythromycin, and chloramphenicol) was performed, aimed at determining and comparing the responses of this model organism to antibiotics at the transcriptional level. On average, 39.71% of genes were differentially regulated by antibiotics at concentrations that inhibit 50% growth. Kanamycin leads to the strongest transcriptomic response (76.4% of genes regulated), whereas polymyxin E led to minimal transcriptomic response (4.7% of genes regulated). Further GO, KEGG, and EcoCyc enrichment analysis found significant transcriptomic changes in carbon metabolism, amino acid metabolism, nutrient assimilation, transport, stress response, nucleotide metabolism, protein biosynthesis, cell wall biosynthesis, energy conservation, mobility, and cell-environmental communications. Analysis of coregulated genes led to the finding of significant reduction of sulfur metabolism by all antibiotics, and analysis of transcription factor-coding genes suggested clustered regulatory patterns implying coregulation. In-depth analysis of regulated pathways revealed shared and unique strategies of E. coli resisting antibiotics, leading to the proposal of four different strategies (the pessimistic, the ignorant, the defensive, and the invasive). In conclusion, this work provides a comprehensive analysis of E. coli’s transcriptomic response to antibiotics, which paves the road for further physiological investigation. IMPORTANCE Antibiotics are among the most important inventions in the history of humankind. They are the ultimate reason why bacterial infections are no longer the number one threat to people’s lives. However, the wide application of antibiotics in the last half a century has led to aggravating antibiotic resistance, weakening the efficacy of antibiotics. To better comprehend the ways bacteria deal with antibiotics that may eventually turn into resistance mechanisms, and to identify good targets for potential antibiotics, knowledge on how bacteria regulate their physiology in response to different classes of antibiotics is needed. This work aimed to fill this knowledge gap by identifying changes of bacterial functions at the transcription level and suggesting strategies of bacteria to resist antibiotics. American Society for Microbiology 2023-02-28 /pmc/articles/PMC10100721/ /pubmed/36853057 http://dx.doi.org/10.1128/spectrum.00317-23 Text en Copyright © 2023 Bie et al. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International license (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Research Article
Bie, Luyao
Zhang, Mengge
Wang, Juan
Fang, Meng
Li, Ling
Xu, Hai
Wang, Mingyu
Comparative Analysis of Transcriptomic Response of Escherichia coli K-12 MG1655 to Nine Representative Classes of Antibiotics
title Comparative Analysis of Transcriptomic Response of Escherichia coli K-12 MG1655 to Nine Representative Classes of Antibiotics
title_full Comparative Analysis of Transcriptomic Response of Escherichia coli K-12 MG1655 to Nine Representative Classes of Antibiotics
title_fullStr Comparative Analysis of Transcriptomic Response of Escherichia coli K-12 MG1655 to Nine Representative Classes of Antibiotics
title_full_unstemmed Comparative Analysis of Transcriptomic Response of Escherichia coli K-12 MG1655 to Nine Representative Classes of Antibiotics
title_short Comparative Analysis of Transcriptomic Response of Escherichia coli K-12 MG1655 to Nine Representative Classes of Antibiotics
title_sort comparative analysis of transcriptomic response of escherichia coli k-12 mg1655 to nine representative classes of antibiotics
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10100721/
https://www.ncbi.nlm.nih.gov/pubmed/36853057
http://dx.doi.org/10.1128/spectrum.00317-23
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