An essential, kinetoplastid-specific GDP-Fuc: β-D-Gal α-1,2-fucosyltransferase is located in the mitochondrion of Trypanosoma brucei

  1. Giulia Bandini
  2. Sebastian Damerow
  3. Maria Lucia Sempaio Güther
  4. Hongjie Guo
  5. Angela Mehlert
  6. Jose Carlos Paredes Franco
  7. Stephen Beverley
  8. Michael A J Ferguson  Is a corresponding author
  1. University of York, United Kingdom
  2. University of Dundee, United Kingdom
  3. Washington University School of Medicine, United States

Abstract

Fucose is a common component of eukaryotic cell-surface glycoconjugates, generally added by Golgi-resident fucosyltransferases. Whereas fucosylated glycoconjugates are rare in kinetoplastids, the biosynthesis of the nucleotide sugar GDP-Fuc has been shown to be essential in Trypanosoma brucei. Here we show that the single identifiable T. brucei fucosyltransferase (TbFUT1) is a GDP-Fuc: β-D-galactose α-1,2-fucosyltransferase with an apparent preference for a Galβ1,3GlcNAcβ1-O-R acceptor motif. Conditional null mutants of TbFUT1 demonstrated that it is essential for both the mammalian-infective bloodstream form and the insect vector-dwelling procyclic form. Unexpectedly, TbFUT1 was localized in the mitochondrion of T. brucei and found to be required for mitochondrial function in bloodstream form trypanosomes. Finally, the TbFUT1 gene was able to complement a Leishmania major mutant lacking the homologous fucosyltransferase gene (Guo et al., 2021). Together these results suggest that kinetoplastids possess an unusual, conserved and essential mitochondrial fucosyltransferase activity that may have therapeutic potential across trypanosomatids.

Data availability

All data in available in the manuscript. No sequencing, proteomics or protein structural data were generated.

Article and author information

Author details

  1. Giulia Bandini

    University of York, York, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-8885-3643
  2. Sebastian Damerow

    University of Dundee, Dundee, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  3. Maria Lucia Sempaio Güther

    University of Dundee, Dundee, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  4. Hongjie Guo

    Washington University School of Medicine, St Louis, United States
    Competing interests
    The authors declare that no competing interests exist.
  5. Angela Mehlert

    University of Dundee, Dundee, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  6. Jose Carlos Paredes Franco

    University of Dundee, Dundee, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  7. Stephen Beverley

    Washington University School of Medicine, St Louis, United States
    Competing interests
    The authors declare that no competing interests exist.
  8. Michael A J Ferguson

    University of Dundee, Dundee, United Kingdom
    For correspondence
    m.a.j.ferguson@dundee.ac.uk
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-1321-8714

Funding

Wellcome Trust (101842)

  • Michael A J Ferguson

National Institute of Allergy and Infectious Diseases (R01-AI31078)

  • Stephen Beverley

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Reviewing Editor

  1. Malcolm J McConville, The University of Melbourne, Australia

Publication history

  1. Received: May 12, 2021
  2. Preprint posted: May 15, 2021 (view preprint)
  3. Accepted: August 15, 2021
  4. Accepted Manuscript published: August 19, 2021 (version 1)
  5. Version of Record published: September 14, 2021 (version 2)

Copyright

© 2021, Bandini et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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  1. Giulia Bandini
  2. Sebastian Damerow
  3. Maria Lucia Sempaio Güther
  4. Hongjie Guo
  5. Angela Mehlert
  6. Jose Carlos Paredes Franco
  7. Stephen Beverley
  8. Michael A J Ferguson
(2021)
An essential, kinetoplastid-specific GDP-Fuc: β-D-Gal α-1,2-fucosyltransferase is located in the mitochondrion of Trypanosoma brucei
eLife 10:e70272.
https://doi.org/10.7554/eLife.70272

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