Chemical genetic screening identifies critical pathways in anthrax lethal toxin-induced pathogenesis.
Chem Biol
; 14(3): 245-55, 2007 Mar.
Article
en En
| MEDLINE
| ID: mdl-17379140
ABSTRACT
Anthrax lethal toxin (LT)-induced cell death via mitogen-activated protein kinase kinase (MAPKK) cleavage remains questionable. Here, a chemical genetics approach was used to investigate what pathways mediate LT-induced cell death. Several small molecules were found to protect macrophages from anthrax LT cytotoxicity and MAPKK from cleavage by lethal factor (LF), without inhibiting LF enzymatic activity or cellular proteasome activity. Interestingly, the compounds activated MAPK-signaling molecules, induced proinflammatory cytokine production, and inhibited LT-induced macrophage apoptosis in a concentration-dependent manner. We propose that induction of antiapoptotic responses by MAPK-dependent or -independent pathways and activation of host innate responses may protect macrophages from anthrax LT-induced cell death. Altering host responses through a chemical genetics approach can help identify critical cellular pathways involved in the pathogenesis of anthrax and can be exploited to further explore host-pathogen interactions.
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Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Toxinas Bacterianas
/
Quinasas de Proteína Quinasa Activadas por Mitógenos
/
Antígenos Bacterianos
Tipo de estudio:
Diagnostic_studies
/
Etiology_studies
/
Prognostic_studies
/
Screening_studies
Límite:
Animals
Idioma:
En
Revista:
Chem Biol
Asunto de la revista:
BIOLOGIA
/
BIOQUIMICA
/
QUIMICA
Año:
2007
Tipo del documento:
Article
País de afiliación:
Estados Unidos