Potent inhibitors of anthrax lethal factor from green tea.
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.
Dell'Aica
Isabella
I
Dipartimento di Scienze Biomediche, Università di Padova, Viale G Colombo 3, 35121 Padua, Italy.
Donà
Massimo
M
Tonello
Fiorella
F
Piris
Alejandro
A
Mock
Michèle
M
Montecucco
Cesare
C
Garbisa
Spiridione
S
D000818:Animals; D000942:Antigens, Bacterial; D017209:Apoptosis / Q000187:drug effects; D001427:Bacterial Toxins / Q000037:antagonists & inhibitors*; D028241:Camellia sinensis / Q000378:metabolism*; D002392:Catechin / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology; D008264:Macrophages / Q000187:drug effects; D045726:Metalloproteases / Q000037:antagonists & inhibitors*; D020929:Mitogen-Activated Protein Kinase Kinases / Q000378:metabolism; D051381:Rats; D011916:Rats, Inbred F344; D013662:Tea / Q000378:metabolism
D000942:Antigens, Bacterial; D001427:Bacterial Toxins; D013662:Tea; C030325:anthrax toxin; D002392:Catechin; C045651:epigallocatechin gallate; D020929:Mitogen-Activated Protein Kinase Kinases; D045726:Metalloproteases