Key tissue targets responsible for anthrax-toxin-induced lethality.
Nature
; 501(7465): 63-8, 2013 Sep 05.
Article
em En
| MEDLINE
| ID: mdl-23995686
ABSTRACT
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.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Contexto em Saúde:
3_ND
Problema de saúde:
3_neglected_diseases
/
3_zoonosis
Assunto principal:
Bacillus anthracis
/
Toxinas Bacterianas
/
Antígenos de Bactérias
Idioma:
En
Revista:
Nature
Ano de publicação:
2013
Tipo de documento:
Article
País de afiliação:
Estados Unidos