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Molecular Mechanisms Underpinning the Circulation and Cellular Uptake of Mycobacterium ulcerans Toxin Mycolactone.
Tello Rubio, Bruno; Bugault, Florence; Baudon, Blandine; Raynal, Bertrand; Brûlé, Sébastien; Morel, Jean-David; Saint-Auret, Sarah; Blanchard, Nicolas; Demangel, Caroline; Guenin-Macé, Laure.
Afiliación
  • Tello Rubio B; Immunobiology of Infection Unit, INSERM U1221, Institut Pasteur, Paris, France.
  • Bugault F; Immunobiology of Infection Unit, INSERM U1221, Institut Pasteur, Paris, France.
  • Baudon B; Immunobiology of Infection Unit, INSERM U1221, Institut Pasteur, Paris, France.
  • Raynal B; Plateforme de Biophysique Moléculaire, UMR 3528 CNRS, Institut Pasteur, Paris, France.
  • Brûlé S; Plateforme de Biophysique Moléculaire, UMR 3528 CNRS, Institut Pasteur, Paris, France.
  • Morel JD; Immunobiology of Infection Unit, INSERM U1221, Institut Pasteur, Paris, France.
  • Saint-Auret S; CNRS, LIMA, UMR 7042, Université de Haute-Alsace, Université de Strasbourg, Mulhouse, France.
  • Blanchard N; CNRS, LIMA, UMR 7042, Université de Haute-Alsace, Université de Strasbourg, Mulhouse, France.
  • Demangel C; Immunobiology of Infection Unit, INSERM U1221, Institut Pasteur, Paris, France.
  • Guenin-Macé L; Immunobiology of Infection Unit, INSERM U1221, Institut Pasteur, Paris, France.
Front Pharmacol ; 12: 733496, 2021.
Article en En | MEDLINE | ID: mdl-34603049
Mycolactone is a diffusible lipid toxin produced by Mycobacterium ulcerans, the causative agent of Buruli ulcer disease. Altough bacterially derived mycolactone has been shown to traffic from cutaneous foci of infection to the bloodstream, the mechanisms underpinning its access to systemic circulation and import by host cells remain largely unknown. Using biophysical and cell-based approaches, we demonstrate that mycolactone specific association to serum albumin and lipoproteins is necessary for its solubilization and is a major mechanism to regulate its bioavailability. We also demonstrate that Scavenger Receptor (SR)-B1 contributes to the cellular uptake of mycolactone. Overall, we suggest a new mechanism of transport and cell entry, challenging the dogma that the toxin enters host cells via passive diffusion.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: Front Pharmacol Año: 2021 Tipo del documento: Article País de afiliación: Francia Pais de publicación: Suiza
Texto completo
Añadir a Mi BVS
Imprimir
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PubMed Links
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: Front Pharmacol Año: 2021 Tipo del documento: Article País de afiliación: Francia Pais de publicación: Suiza