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Genome-scale model of metabolism and gene expression provides a multi-scale description of acid stress responses in Escherichia coli
Response to acid stress is critical for Escherichia coli to successfully complete its life-cycle by passing through the stomach to colonize the digestive tract. To develop a fundamental understanding of this response, we established a molecular mechanistic description of acid stress mitigation respo...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6897400/ https://www.ncbi.nlm.nih.gov/pubmed/31809503 http://dx.doi.org/10.1371/journal.pcbi.1007525 |
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author | Du, Bin Yang, Laurence Lloyd, Colton J. Fang, Xin Palsson, Bernhard O. |
author_facet | Du, Bin Yang, Laurence Lloyd, Colton J. Fang, Xin Palsson, Bernhard O. |
author_sort | Du, Bin |
collection | PubMed |
description | Response to acid stress is critical for Escherichia coli to successfully complete its life-cycle by passing through the stomach to colonize the digestive tract. To develop a fundamental understanding of this response, we established a molecular mechanistic description of acid stress mitigation responses in E. coli and integrated them with a genome-scale model of its metabolism and macromolecular expression (ME-model). We considered three known mechanisms of acid stress mitigation: 1) change in membrane lipid fatty acid composition, 2) change in periplasmic protein stability over external pH and periplasmic chaperone protection mechanisms, and 3) change in the activities of membrane proteins. After integrating these mechanisms into an established ME-model, we could simulate their responses in the context of other cellular processes. We validated these simulations using RNA sequencing data obtained from five E. coli strains grown under external pH ranging from 5.5 to 7.0. We found: i) that for the differentially expressed genes accounted for in the ME-model, 80% of the upregulated genes were correctly predicted by the ME-model, and ii) that these genes are mainly involved in translation processes (45% of genes), membrane proteins and related processes (18% of genes), amino acid metabolism (12% of genes), and cofactor and prosthetic group biosynthesis (8% of genes). We also demonstrated several intervention strategies on acid tolerance that can be simulated by the ME-model. We thus established a quantitative framework that describes, on a genome-scale, the acid stress mitigation response of E. coli that has both scientific and practical uses. |
format | Online Article Text |
id | pubmed-6897400 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-68974002019-12-13 Genome-scale model of metabolism and gene expression provides a multi-scale description of acid stress responses in Escherichia coli Du, Bin Yang, Laurence Lloyd, Colton J. Fang, Xin Palsson, Bernhard O. PLoS Comput Biol Research Article Response to acid stress is critical for Escherichia coli to successfully complete its life-cycle by passing through the stomach to colonize the digestive tract. To develop a fundamental understanding of this response, we established a molecular mechanistic description of acid stress mitigation responses in E. coli and integrated them with a genome-scale model of its metabolism and macromolecular expression (ME-model). We considered three known mechanisms of acid stress mitigation: 1) change in membrane lipid fatty acid composition, 2) change in periplasmic protein stability over external pH and periplasmic chaperone protection mechanisms, and 3) change in the activities of membrane proteins. After integrating these mechanisms into an established ME-model, we could simulate their responses in the context of other cellular processes. We validated these simulations using RNA sequencing data obtained from five E. coli strains grown under external pH ranging from 5.5 to 7.0. We found: i) that for the differentially expressed genes accounted for in the ME-model, 80% of the upregulated genes were correctly predicted by the ME-model, and ii) that these genes are mainly involved in translation processes (45% of genes), membrane proteins and related processes (18% of genes), amino acid metabolism (12% of genes), and cofactor and prosthetic group biosynthesis (8% of genes). We also demonstrated several intervention strategies on acid tolerance that can be simulated by the ME-model. We thus established a quantitative framework that describes, on a genome-scale, the acid stress mitigation response of E. coli that has both scientific and practical uses. Public Library of Science 2019-12-06 /pmc/articles/PMC6897400/ /pubmed/31809503 http://dx.doi.org/10.1371/journal.pcbi.1007525 Text en © 2019 Du et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
spellingShingle | Research Article Du, Bin Yang, Laurence Lloyd, Colton J. Fang, Xin Palsson, Bernhard O. Genome-scale model of metabolism and gene expression provides a multi-scale description of acid stress responses in Escherichia coli |
title | Genome-scale model of metabolism and gene expression provides a multi-scale description of acid stress responses in Escherichia coli |
title_full | Genome-scale model of metabolism and gene expression provides a multi-scale description of acid stress responses in Escherichia coli |
title_fullStr | Genome-scale model of metabolism and gene expression provides a multi-scale description of acid stress responses in Escherichia coli |
title_full_unstemmed | Genome-scale model of metabolism and gene expression provides a multi-scale description of acid stress responses in Escherichia coli |
title_short | Genome-scale model of metabolism and gene expression provides a multi-scale description of acid stress responses in Escherichia coli |
title_sort | genome-scale model of metabolism and gene expression provides a multi-scale description of acid stress responses in escherichia coli |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6897400/ https://www.ncbi.nlm.nih.gov/pubmed/31809503 http://dx.doi.org/10.1371/journal.pcbi.1007525 |
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