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A genome-scale metabolic model of parasitic whipworm
Genome-scale metabolic models are widely used to enhance our understanding of metabolic features of organisms, host-pathogen interactions and to identify therapeutics for diseases. Here we present iTMU798, the genome-scale metabolic model of the mouse whipworm Trichuris muris. The model demonstrates...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10618284/ https://www.ncbi.nlm.nih.gov/pubmed/37907472 http://dx.doi.org/10.1038/s41467-023-42552-4 |
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author | Bay, Ömer F. Hayes, Kelly S. Schwartz, Jean-Marc Grencis, Richard K. Roberts, Ian S. |
author_facet | Bay, Ömer F. Hayes, Kelly S. Schwartz, Jean-Marc Grencis, Richard K. Roberts, Ian S. |
author_sort | Bay, Ömer F. |
collection | PubMed |
description | Genome-scale metabolic models are widely used to enhance our understanding of metabolic features of organisms, host-pathogen interactions and to identify therapeutics for diseases. Here we present iTMU798, the genome-scale metabolic model of the mouse whipworm Trichuris muris. The model demonstrates the metabolic features of T. muris and allows the prediction of metabolic steps essential for its survival. Specifically, that Thioredoxin Reductase (TrxR) enzyme is essential, a prediction we validate in vitro with the drug auranofin. Furthermore, our observation that the T. muris genome lacks gsr-1 encoding Glutathione Reductase (GR) but has GR activity that can be inhibited by auranofin indicates a mechanism for the reduction of glutathione by the TrxR enzyme in T. muris. In addition, iTMU798 predicts seven essential amino acids that cannot be synthesised by T. muris, a prediction we validate for the amino acid tryptophan. Overall, iTMU798 is as a powerful tool to study not only the T. muris metabolism but also other Trichuris spp. in understanding host parasite interactions and the rationale design of new intervention strategies. |
format | Online Article Text |
id | pubmed-10618284 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-106182842023-11-02 A genome-scale metabolic model of parasitic whipworm Bay, Ömer F. Hayes, Kelly S. Schwartz, Jean-Marc Grencis, Richard K. Roberts, Ian S. Nat Commun Article Genome-scale metabolic models are widely used to enhance our understanding of metabolic features of organisms, host-pathogen interactions and to identify therapeutics for diseases. Here we present iTMU798, the genome-scale metabolic model of the mouse whipworm Trichuris muris. The model demonstrates the metabolic features of T. muris and allows the prediction of metabolic steps essential for its survival. Specifically, that Thioredoxin Reductase (TrxR) enzyme is essential, a prediction we validate in vitro with the drug auranofin. Furthermore, our observation that the T. muris genome lacks gsr-1 encoding Glutathione Reductase (GR) but has GR activity that can be inhibited by auranofin indicates a mechanism for the reduction of glutathione by the TrxR enzyme in T. muris. In addition, iTMU798 predicts seven essential amino acids that cannot be synthesised by T. muris, a prediction we validate for the amino acid tryptophan. Overall, iTMU798 is as a powerful tool to study not only the T. muris metabolism but also other Trichuris spp. in understanding host parasite interactions and the rationale design of new intervention strategies. Nature Publishing Group UK 2023-10-31 /pmc/articles/PMC10618284/ /pubmed/37907472 http://dx.doi.org/10.1038/s41467-023-42552-4 Text en © The Author(s) 2023 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Article Bay, Ömer F. Hayes, Kelly S. Schwartz, Jean-Marc Grencis, Richard K. Roberts, Ian S. A genome-scale metabolic model of parasitic whipworm |
title | A genome-scale metabolic model of parasitic whipworm |
title_full | A genome-scale metabolic model of parasitic whipworm |
title_fullStr | A genome-scale metabolic model of parasitic whipworm |
title_full_unstemmed | A genome-scale metabolic model of parasitic whipworm |
title_short | A genome-scale metabolic model of parasitic whipworm |
title_sort | genome-scale metabolic model of parasitic whipworm |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10618284/ https://www.ncbi.nlm.nih.gov/pubmed/37907472 http://dx.doi.org/10.1038/s41467-023-42552-4 |
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