To carry out their activities, Research Teams of the Frédéric Joliot Institute for Life Sciences have developed high-profile technological platforms in many areas : biomedical imaging, structural biology, metabolomics, High-Throughput screening, level 3 microbiological safety laboratory...
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Scientific result | Health ＆ life sciences | High-throughput screening | Bacteria
A SIMOPRO Research Team, in collaboration with a SCBM Team, has identified, by screening a library of small chemical molecules, a compound capable of reducing the sensitivity of cells to a plant toxin, that is ricin. By collaborating with seven Teams of microbiologists, researchers have shown that this compound, called ABMA, protects cells by blocking an intracellular transport pathway borrowed by many other bacterial and intracellular pathogenic toxins. ABMA defines a new family of broad-spectrum anti-infective agents.
Intracellular pathogenic microorganisms and toxins exploit host cell mechanisms to enter, exert their deleterious effects as well as hijack host nutrition for their development. A potential approach to treat multiple pathogen infections and that should not induce drug resistance is the use of small molecules that target host components. We identified the compound 1-adamantyl (5-bromo-2-methoxybenzyl) amine (ABMA) from a cell-based high throughput screening for its capacity to protect human cells and mice against ricin toxin without toxicity. This compound efficiently protects cells against various toxins and pathogens including viruses, intracellular bacteria and parasite. ABMA provokes Rab7-positive late endosomal compartment accumulation in mammalian cells without affecting other organelles (early endosomes, lysosomes, the Golgi apparatus, the endoplasmic reticulum or the nucleus). As the mechanism of action of ABMA is restricted to host-endosomal compartments, it reduces cell infection by pathogens that depend on this pathway to invade cells. ABMA may represent a novel class of broad-spectrum compounds with therapeutic potential against diverse severe infectious diseases.
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Référence : Wu, Y, Pons V, Goudet A, Panigai L, Fischer A, Herweg JA, Kali S, Davey RA, Laporte J, Bouclier C, Yousfi R, Aubenque C, Merer G, Gobbo E, Lopez R, Gillet C, Cojean S, Popoff MR, Clayette P, Le Grand R, Boulogne C, Tordo N, Lemichez E, Loiseau PM, Rudel T, Sauvaire D, Cintrat JC, Gillet D, Barbier J. (2017) ABMA, a small molecule that inhibits intracellular toxins and pathogens by interfering with late endosomal compartments. Sci. Rep. 7:15567 http://dx.doi.org/10.1038/s41598-017-15466-7
CEA is a French government-funded technological research organisation in four main areas: low-carbon energies, defense and security, information technologies and health technologies. A prominent player in the European Research Area, it is involved in setting up collaborative projects with many partners around the world.