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Mechanism of Trypanosoma brucei gambiense resistance to human serum

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  • Pierrick Uzureau

    (Laboratory of Molecular Parasitology, IBMM, Université Libre de Bruxelles (ULB), 12 rue des Prof. Jeener et Brachet, B-6041 Gosselies, Belgium)

  • Sophie Uzureau

    (Laboratory of Molecular Parasitology, IBMM, Université Libre de Bruxelles (ULB), 12 rue des Prof. Jeener et Brachet, B-6041 Gosselies, Belgium)

  • Laurence Lecordier

    (Laboratory of Molecular Parasitology, IBMM, Université Libre de Bruxelles (ULB), 12 rue des Prof. Jeener et Brachet, B-6041 Gosselies, Belgium)

  • Frédéric Fontaine

    (Laboratory of Molecular Parasitology, IBMM, Université Libre de Bruxelles (ULB), 12 rue des Prof. Jeener et Brachet, B-6041 Gosselies, Belgium)

  • Patricia Tebabi

    (Laboratory of Molecular Parasitology, IBMM, Université Libre de Bruxelles (ULB), 12 rue des Prof. Jeener et Brachet, B-6041 Gosselies, Belgium)

  • Fabrice Homblé

    (Structure and Function of Biological Membranes, Université Libre de Bruxelles, B-1050 Brussels, Belgium)

  • Axelle Grélard

    (Institute of Chemistry & Biology of Membranes & Nanoobjects, UMR 5248, CNRS, Université Bordeaux, Institut Polytechnique Bordeaux, F-33600 Pessac, France)

  • Vanessa Zhendre

    (Institute of Chemistry & Biology of Membranes & Nanoobjects, UMR 5248, CNRS, Université Bordeaux, Institut Polytechnique Bordeaux, F-33600 Pessac, France)

  • Derek P. Nolan

    (Molecular Parasitology Group, School of Biochemistry and Immunology, Trinity College Dublin, Dublin 2, Ireland)

  • Laurence Lins

    (Center of Numerical Molecular Biophysics, Université de Liège, B-5030 Gembloux, Belgium)

  • Jean-Marc Crowet

    (Center of Numerical Molecular Biophysics, Université de Liège, B-5030 Gembloux, Belgium)

  • Annette Pays

    (Laboratory of Molecular Parasitology, IBMM, Université Libre de Bruxelles (ULB), 12 rue des Prof. Jeener et Brachet, B-6041 Gosselies, Belgium)

  • Cécile Felu

    (Laboratory of Molecular Parasitology, IBMM, Université Libre de Bruxelles (ULB), 12 rue des Prof. Jeener et Brachet, B-6041 Gosselies, Belgium)

  • Philippe Poelvoorde

    (Laboratory of Molecular Parasitology, IBMM, Université Libre de Bruxelles (ULB), 12 rue des Prof. Jeener et Brachet, B-6041 Gosselies, Belgium)

  • Benoit Vanhollebeke

    (Laboratory of Molecular Parasitology, IBMM, Université Libre de Bruxelles (ULB), 12 rue des Prof. Jeener et Brachet, B-6041 Gosselies, Belgium)

  • Soren K. Moestrup

    (University of Aarhus)

  • Jeppe Lyngsø

    (University of Aarhus, DK-8000 Aarhus, Denmark)

  • Jan Skov Pedersen

    (University of Aarhus, DK-8000 Aarhus, Denmark)

  • Jeremy C. Mottram

    (Wellcome Trust Centre for Molecular Parasitology, University of Glasgow, Glasgow G12 8TA, UK)

  • Erick J. Dufourc

    (Institute of Chemistry & Biology of Membranes & Nanoobjects, UMR 5248, CNRS, Université Bordeaux, Institut Polytechnique Bordeaux, F-33600 Pessac, France)

  • David Pérez-Morga

    (Center for Microscopy and Molecular Imaging (CMMI) and Laboratory of Molecular Parasitology, IBMM, Université Libre de Bruxelles, B-6041 Gosselies, Belgium)

  • Etienne Pays

    (Walloon Excellence in Life sciences and Biotechnology (WELBIO) and Laboratory of Molecular Parasitology, IBMM, Université Libre de Bruxelles, B-6041 Gosselies, Belgium)

Abstract

This study shows that Trypanosoma brucei gambiense resists trypanolytic factors (TLFs) in a multifactorial manner, relying on a hydrophobic β-sheet of the TgsGP glycoprotein, which prevents APOL1 toxicity and induces membrane stiffening, as well as a reduction in sensitivity to APOL1 requiring cysteine protease activity and TLF-1 receptor inactivation owing to a single amino acid substitution.

Suggested Citation

  • Pierrick Uzureau & Sophie Uzureau & Laurence Lecordier & Frédéric Fontaine & Patricia Tebabi & Fabrice Homblé & Axelle Grélard & Vanessa Zhendre & Derek P. Nolan & Laurence Lins & Jean-Marc Crowet & A, 2013. "Mechanism of Trypanosoma brucei gambiense resistance to human serum," Nature, Nature, vol. 501(7467), pages 430-434, September.
    • Handle: RePEc:nat:nature:v:501:y:2013:i:7467:d:10.1038_nature12516
    DOI: 10.1038/nature12516
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    Cited by:

    1. Hagen Sülzen & Jakub Began & Arun Dhillon & Sami Kereïche & Petr Pompach & Jitka Votrubova & Farnaz Zahedifard & Adriana Šubrtova & Marie Šafner & Martin Hubalek & Maaike Thompson & Martin Zoltner & S, 2023. "Cryo-EM structures of Trypanosoma brucei gambiense ISG65 with human complement C3 and C3b and their roles in alternative pathway restriction," Nature Communications, Nature, vol. 14(1), pages 1-18, December.
    2. Eva Horáková & Laurence Lecordier & Paula Cunha & Roman Sobotka & Piya Changmai & Catharina J. M. Langedijk & Jan Van Den Abbeele & Benoit Vanhollebeke & Julius Lukeš, 2022. "Heme-deficient metabolism and impaired cellular differentiation as an evolutionary trade-off for human infectivity in Trypanosoma brucei gambiense," Nature Communications, Nature, vol. 13(1), pages 1-14, December.

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