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A curated genome-scale metabolic model of Bordetella pertussis metabolism

The Gram-negative bacterium Bordetella pertussis is the causative agent of whooping cough, a serious respiratory infection causing hundreds of thousands of deaths annually worldwide. There are effective vaccines, but their production requires growing large quantities of B. pertussis. Unfortunately,...

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Detalles Bibliográficos
Autores principales: Fyson, Nick, King, Jerry, Belcher, Thomas, Preston, Andrew, Colijn, Caroline
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5553986/
https://www.ncbi.nlm.nih.gov/pubmed/28715411
http://dx.doi.org/10.1371/journal.pcbi.1005639
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author Fyson, Nick
King, Jerry
Belcher, Thomas
Preston, Andrew
Colijn, Caroline
author_facet Fyson, Nick
King, Jerry
Belcher, Thomas
Preston, Andrew
Colijn, Caroline
author_sort Fyson, Nick
collection PubMed
description The Gram-negative bacterium Bordetella pertussis is the causative agent of whooping cough, a serious respiratory infection causing hundreds of thousands of deaths annually worldwide. There are effective vaccines, but their production requires growing large quantities of B. pertussis. Unfortunately, B. pertussis has relatively slow growth in culture, with low biomass yields and variable growth characteristics. B. pertussis also requires a relatively expensive growth medium. We present a new, curated flux balance analysis-based model of B. pertussis metabolism. We enhance the model with an experimentally-determined biomass objective function, and we perform extensive manual curation. We test the model’s predictions with a genome-wide screen for essential genes using a transposon-directed insertional sequencing (TraDIS) approach. We test its predictions of growth for different carbon sources in the medium. The model predicts essentiality with an accuracy of 83% and correctly predicts improvements in growth under increased glutamate:fumarate ratios. We provide the model in SBML format, along with gene essentiality predictions.
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spelling pubmed-55539862017-08-25 A curated genome-scale metabolic model of Bordetella pertussis metabolism Fyson, Nick King, Jerry Belcher, Thomas Preston, Andrew Colijn, Caroline PLoS Comput Biol Research Article The Gram-negative bacterium Bordetella pertussis is the causative agent of whooping cough, a serious respiratory infection causing hundreds of thousands of deaths annually worldwide. There are effective vaccines, but their production requires growing large quantities of B. pertussis. Unfortunately, B. pertussis has relatively slow growth in culture, with low biomass yields and variable growth characteristics. B. pertussis also requires a relatively expensive growth medium. We present a new, curated flux balance analysis-based model of B. pertussis metabolism. We enhance the model with an experimentally-determined biomass objective function, and we perform extensive manual curation. We test the model’s predictions with a genome-wide screen for essential genes using a transposon-directed insertional sequencing (TraDIS) approach. We test its predictions of growth for different carbon sources in the medium. The model predicts essentiality with an accuracy of 83% and correctly predicts improvements in growth under increased glutamate:fumarate ratios. We provide the model in SBML format, along with gene essentiality predictions. Public Library of Science 2017-07-17 /pmc/articles/PMC5553986/ /pubmed/28715411 http://dx.doi.org/10.1371/journal.pcbi.1005639 Text en © 2017 Fyson 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
Fyson, Nick
King, Jerry
Belcher, Thomas
Preston, Andrew
Colijn, Caroline
A curated genome-scale metabolic model of Bordetella pertussis metabolism
title A curated genome-scale metabolic model of Bordetella pertussis metabolism
title_full A curated genome-scale metabolic model of Bordetella pertussis metabolism
title_fullStr A curated genome-scale metabolic model of Bordetella pertussis metabolism
title_full_unstemmed A curated genome-scale metabolic model of Bordetella pertussis metabolism
title_short A curated genome-scale metabolic model of Bordetella pertussis metabolism
title_sort curated genome-scale metabolic model of bordetella pertussis metabolism
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5553986/
https://www.ncbi.nlm.nih.gov/pubmed/28715411
http://dx.doi.org/10.1371/journal.pcbi.1005639
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