Mechanism of Trypanosoma brucei gambiense resistance to human serum

Pierrick Uzureau, Sophie Uzureau, Laurence Lecordier, Frédéric Fontaine, Patricia Tebabi, Fabrice Homblé, Axelle Grélard, Vanessa Zhendre, Derek P. Nolan, Laurence Lins, Jean-Marc Crowet, Annette Pays, Cécile Felu, Philippe Poelvoorde, Benoit Vanhollebeke, Soren K. Moestrup, Jeppe Lyngsø, Jan Skov Pedersen, Jeremy C. Mottram, Erick J. Dufourc, David Pérez-Morga and Etienne Pays ()
Additional contact information
Pierrick 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

Nature, 2013, vol. 501, issue 7467, 430-434

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.

Date: 2013
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DOI: 10.1038/nature12516

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