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Publication : Key tissue targets responsible for anthrax-toxin-induced lethality.

First Author  Liu S Year  2013
Journal  Nature Volume  501
Issue  7465 Pages  63-8
PubMed ID  23995686 Mgi Jnum  J:205421
Mgi Id  MGI:5544852 Doi  10.1038/nature12510
Citation  Liu S, et al. (2013) Key tissue targets responsible for anthrax-toxin-induced lethality. Nature 501(7465):63-8
abstractText  Bacillus anthracis, the causative agent of anthrax disease, is lethal owing to the actions of two exotoxins: anthrax lethal toxin (LT) and oedema toxin (ET). The key tissue targets responsible for the lethal effects of these toxins are unknown. Here we generated cell-type-specific anthrax toxin receptor capillary morphogenesis protein-2 (CMG2)-null mice and cell-type-specific CMG2-expressing mice and challenged them with the toxins. Our results show that lethality induced by LT and ET occurs through damage to distinct cell types; whereas targeting cardiomyocytes and vascular smooth muscle cells is required for LT-induced mortality, ET-induced lethality occurs mainly through its action in hepatocytes. Notably, and in contradiction to what has been previously postulated, targeting of endothelial cells by either toxin does not seem to contribute significantly to lethality. Our findings demonstrate that B. anthracis has evolved to use LT and ET to induce host lethality by coordinately damaging two distinct vital systems.
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