Molecular Mechanisms Underpinning the Circulation and Cellular Uptake of Mycobacterium ulcerans Toxin Mycolactone
| Autor: | Bruno Tello Rubio, Florence Bugault, Blandine Baudon, Bertrand Raynal, Sébastien Brûlé, Jean-David Morel, Sarah Saint-Auret, Nicolas Blanchard, Caroline Demangel, Laure Guenin-Macé |
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| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: | |
| Zdroj: | Frontiers in Pharmacology, Vol 12 (2021) |
| Druh dokumentu: | article |
| ISSN: | 1663-9812 37029746 |
| DOI: | 10.3389/fphar.2021.733496 |
| Popis: | 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. |
| Databáze: | Directory of Open Access Journals |
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