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Elucidation of Regulatory Modes for Five Two-Component Systems in Escherichia coli Reveals Novel Relationships

Escherichia coli uses two-component systems (TCSs) to respond to environmental signals. TCSs affect gene expression and are parts of E. coli’s global transcriptional regulatory network (TRN). Here, we identified the regulons of five TCSs in E. coli MG1655: BaeSR and CpxAR, which were stimulated by e...

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Autores principales: Choudhary, Kumari Sonal, Kleinmanns, Julia A., Decker, Katherine, Sastry, Anand V., Gao, Ye, Szubin, Richard, Seif, Yara, Palsson, Bernhard O.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Society for Microbiology 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7657598/
https://www.ncbi.nlm.nih.gov/pubmed/33172971
http://dx.doi.org/10.1128/mSystems.00980-20
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author Choudhary, Kumari Sonal
Kleinmanns, Julia A.
Decker, Katherine
Sastry, Anand V.
Gao, Ye
Szubin, Richard
Seif, Yara
Palsson, Bernhard O.
author_facet Choudhary, Kumari Sonal
Kleinmanns, Julia A.
Decker, Katherine
Sastry, Anand V.
Gao, Ye
Szubin, Richard
Seif, Yara
Palsson, Bernhard O.
author_sort Choudhary, Kumari Sonal
collection PubMed
description Escherichia coli uses two-component systems (TCSs) to respond to environmental signals. TCSs affect gene expression and are parts of E. coli’s global transcriptional regulatory network (TRN). Here, we identified the regulons of five TCSs in E. coli MG1655: BaeSR and CpxAR, which were stimulated by ethanol stress; KdpDE and PhoRB, induced by limiting potassium and phosphate, respectively; and ZraSR, stimulated by zinc. We analyzed RNA-seq data using independent component analysis (ICA). ChIP-exo data were used to validate condition-specific target gene binding sites. Based on these data, we do the following: (i) identify the target genes for each TCS; (ii) show how the target genes are transcribed in response to stimulus; and (iii) reveal novel relationships between TCSs, which indicate noncognate inducers for various response regulators, such as BaeR to iron starvation, CpxR to phosphate limitation, and PhoB and ZraR to cell envelope stress. Our understanding of the TRN in E. coli is thus notably expanded. IMPORTANCE E. coli is a common commensal microbe found in the human gut microenvironment; however, some strains cause diseases like diarrhea, urinary tract infections, and meningitis. E. coli’s two-component systems (TCSs) modulate target gene expression, especially related to virulence, pathogenesis, and antimicrobial peptides, in response to environmental stimuli. Thus, it is of utmost importance to understand the transcriptional regulation of TCSs to infer bacterial environmental adaptation and disease pathogenicity. Utilizing a combinatorial approach integrating RNA sequencing (RNA-seq), independent component analysis, chromatin immunoprecipitation coupled with exonuclease treatment (ChIP-exo), and data mining, we suggest five different modes of TCS transcriptional regulation. Our data further highlight noncognate inducers of TCSs, which emphasizes the cross-regulatory nature of TCSs in E. coli and suggests that TCSs may have a role beyond their cognate functionalities. In summary, these results can lead to an understanding of the metabolic capabilities of bacteria and correctly predict complex phenotype under diverse conditions, especially when further incorporated with genome-scale metabolic models.
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spelling pubmed-76575982020-11-17 Elucidation of Regulatory Modes for Five Two-Component Systems in Escherichia coli Reveals Novel Relationships Choudhary, Kumari Sonal Kleinmanns, Julia A. Decker, Katherine Sastry, Anand V. Gao, Ye Szubin, Richard Seif, Yara Palsson, Bernhard O. mSystems Research Article Escherichia coli uses two-component systems (TCSs) to respond to environmental signals. TCSs affect gene expression and are parts of E. coli’s global transcriptional regulatory network (TRN). Here, we identified the regulons of five TCSs in E. coli MG1655: BaeSR and CpxAR, which were stimulated by ethanol stress; KdpDE and PhoRB, induced by limiting potassium and phosphate, respectively; and ZraSR, stimulated by zinc. We analyzed RNA-seq data using independent component analysis (ICA). ChIP-exo data were used to validate condition-specific target gene binding sites. Based on these data, we do the following: (i) identify the target genes for each TCS; (ii) show how the target genes are transcribed in response to stimulus; and (iii) reveal novel relationships between TCSs, which indicate noncognate inducers for various response regulators, such as BaeR to iron starvation, CpxR to phosphate limitation, and PhoB and ZraR to cell envelope stress. Our understanding of the TRN in E. coli is thus notably expanded. IMPORTANCE E. coli is a common commensal microbe found in the human gut microenvironment; however, some strains cause diseases like diarrhea, urinary tract infections, and meningitis. E. coli’s two-component systems (TCSs) modulate target gene expression, especially related to virulence, pathogenesis, and antimicrobial peptides, in response to environmental stimuli. Thus, it is of utmost importance to understand the transcriptional regulation of TCSs to infer bacterial environmental adaptation and disease pathogenicity. Utilizing a combinatorial approach integrating RNA sequencing (RNA-seq), independent component analysis, chromatin immunoprecipitation coupled with exonuclease treatment (ChIP-exo), and data mining, we suggest five different modes of TCS transcriptional regulation. Our data further highlight noncognate inducers of TCSs, which emphasizes the cross-regulatory nature of TCSs in E. coli and suggests that TCSs may have a role beyond their cognate functionalities. In summary, these results can lead to an understanding of the metabolic capabilities of bacteria and correctly predict complex phenotype under diverse conditions, especially when further incorporated with genome-scale metabolic models. American Society for Microbiology 2020-11-10 /pmc/articles/PMC7657598/ /pubmed/33172971 http://dx.doi.org/10.1128/mSystems.00980-20 Text en Copyright © 2020 Choudhary 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
Choudhary, Kumari Sonal
Kleinmanns, Julia A.
Decker, Katherine
Sastry, Anand V.
Gao, Ye
Szubin, Richard
Seif, Yara
Palsson, Bernhard O.
Elucidation of Regulatory Modes for Five Two-Component Systems in Escherichia coli Reveals Novel Relationships
title Elucidation of Regulatory Modes for Five Two-Component Systems in Escherichia coli Reveals Novel Relationships
title_full Elucidation of Regulatory Modes for Five Two-Component Systems in Escherichia coli Reveals Novel Relationships
title_fullStr Elucidation of Regulatory Modes for Five Two-Component Systems in Escherichia coli Reveals Novel Relationships
title_full_unstemmed Elucidation of Regulatory Modes for Five Two-Component Systems in Escherichia coli Reveals Novel Relationships
title_short Elucidation of Regulatory Modes for Five Two-Component Systems in Escherichia coli Reveals Novel Relationships
title_sort elucidation of regulatory modes for five two-component systems in escherichia coli reveals novel relationships
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7657598/
https://www.ncbi.nlm.nih.gov/pubmed/33172971
http://dx.doi.org/10.1128/mSystems.00980-20
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