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| HAL : hal-00509058, version 1 |
| PubMed : 20403321 |
| DOI : 10.1016/j.cell.2010.01.043 |
| Fiche détaillée |  Récupérer au format |
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| Cell 141, 2 (2010) 231-42 |
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| Inhibition of retrograde transport protects mice from lethal ricin challenge. |
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| Bahne StechmannSiau-Kun Bai |
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| (16/04/2010) |
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| Bacterial Shiga-like toxins are virulence factors that constitute a significant public health threat worldwide, and the plant toxin ricin is a potential bioterror weapon. To gain access to their cytosolic target, ribosomal RNA, these toxins follow the retrograde transport route from the plasma membrane to the endoplasmic reticulum, via endosomes and the Golgi apparatus. Here, we used high-throughput screening to identify small molecule inhibitors that protect cells from ricin and Shiga-like toxins. We identified two compounds that selectively block retrograde toxin trafficking at the early endosome-TGN interface, without affecting compartment morphology, endogenous retrograde cargos, or other trafficking steps, demonstrating an unexpected degree of selectivity and lack of toxicity. In mice, one compound clearly protects from lethal nasal exposure to ricin. Our work discovers the first small molecule that shows efficacy against ricin in animal experiments and identifies the retrograde route as a potential therapeutic target. |
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| 1 : | Laboratoire de synthèse organique (DCSO) |
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CNRS : UMR7652 – Polytechnique - X |
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| 2 : | Compartimentation et dynamique cellulaires (CDC) |
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CNRS : UMR144 – Institut Curie – Université Pierre et Marie Curie [UPMC] - Paris VI |
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| 3 : | Centre d'études d'agents Pathogènes et Biotechnologies pour la Santé (CPBS) |
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Université Montpellier I – CNRS : UMR5236 – Université Montpellier II - Sciences et techniques |
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| 4 : | Laboratoire de neurobiologie cellulaire et moléculaire (NBCM) |
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CNRS : UPR9040 |
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| Domaine | : | Sciences du Vivant/Microbiologie et Parasitologie/Virologie |
| hal-00509058, version 1 | |
| http://hal.archives-ouvertes.fr/hal-00509058 | |
| oai:hal.archives-ouvertes.fr:hal-00509058 | |
| Contributeur : Nathalie Pasqualini | |
| Soumis le : Mardi 10 Août 2010, 09:14:00 | |
| Dernière modification le : Mercredi 11 Août 2010, 12:36:32 | |
