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A genome-scale metabolic model of parasitic whipworm

Author

Listed:
  • Ömer F. Bay

    (University of Manchester
    Abdullah Gül University
    University of Manchester)

  • Kelly S. Hayes

    (University of Manchester
    University of Manchester
    University of Manchester)

  • Jean-Marc Schwartz

    (University of Manchester)

  • Richard K. Grencis

    (University of Manchester
    University of Manchester
    University of Manchester)

  • Ian S. Roberts

    (University of Manchester
    University of Manchester)

Abstract

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.

Suggested Citation

  • Ömer F. Bay & Kelly S. Hayes & Jean-Marc Schwartz & Richard K. Grencis & Ian S. Roberts, 2023. "A genome-scale metabolic model of parasitic whipworm," Nature Communications, Nature, vol. 14(1), pages 1-10, December.
    • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-42552-4
    DOI: 10.1038/s41467-023-42552-4
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    1. Allison J. Bancroft & Colin W. Levy & Thomas A. Jowitt & Kelly S. Hayes & Seona Thompson & Edward A. Mckenzie & Matthew D. Ball & Eamon Dubaissi & Aidan P. France & Bruno Bellina & Catherine Sharpe & , 2019. "The major secreted protein of the whipworm parasite tethers to matrix and inhibits interleukin-13 function," Nature Communications, Nature, vol. 10(1), pages 1-11, December.
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