RESUMEN
The anthrax lethal factor (LF) has a major role in the development of anthrax. LF is delivered by the protective antigen (PA) inside the cell, where it exerts its metalloprotease activity on the N-terminus of MAPK-kinases. PA+LF are cytotoxic to macrophages in culture and kill the Fischer 344 rat when injected intravenously. We describe here the properties of some polyphenols contained in green tea as powerful inhibitors of LF metalloproteolytic activity, and how the main catechin of green tea, (-)epigallocatechin-3-gallate, prevents the LF-induced death of macrophages and Fischer 344 rats.
Asunto(s)
Toxinas Bacterianas/antagonistas & inhibidores , Camellia sinensis/metabolismo , Catequina/análogos & derivados , Metaloproteasas/antagonistas & inhibidores , Animales , Antígenos Bacterianos , Apoptosis/efectos de los fármacos , Catequina/metabolismo , Catequina/farmacología , Macrófagos/efectos de los fármacos , Quinasas de Proteína Quinasa Activadas por Mitógenos/metabolismo , Ratas , Ratas Endogámicas F344 , Té/metabolismoRESUMEN
The disease anthrax is caused by lethal factor, an enzyme component of the toxin produced by the spore-forming bacterium Bacillus anthracis. Here we describe substrate molecules for this factor that offer a means for high-throughput screening of potential inhibitors for use in anthrax treatment. Our assay should help to answer the urgent call for new and specific therapies to combat this pathogen after its recent emergence as a terrorist bioweapon.