The cytotoxic activity of Bacillus anthracis lethal factor is inhibited by leukotriene A4 hydrolase and metallopeptidase inhibitors.
The lethal factor of Bacillus anthracis is central to the pathogenesis of anthrax. Its mechanism of action is still unknown. Recently, on the basis of sequence similarities, we suggested that lethal factor might act similarly to leukotriene A4 hydrolase (LTA4), a bifunctional enzyme also endowed with a metallopeptidase activity. Here we show that some inhibitors of the LTA4 hydrolase and metallopeptidase activities of LTA4 hydrolase also affect the cytotoxicity of the anthrax lethal factor on macrophage cell lines, without interfering with the ability of the lethal factor to enter cells. These results support the proposal that anthrax lethal factor might display in the cytosol of intoxicated cells a peptidase activity similar to that of LTA4 hydrolase.
Menard
A
A
Centro CNR Biomembrane, Università di Padova, Italy.
Papini
E
E
Mock
M
M
Montecucco
C
C
D000818:Animals; D000942:Antigens, Bacterial; D001408:Bacillus anthracis; D001427:Bacterial Toxins / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000633:toxicity*; D002470:Cell Survival / Q000187:drug effects*; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D004851:Epoxide Hydrolases / Q000037:antagonists & inhibitors*; D007700:Kinetics; D016859:Lipoxygenase Inhibitors / Q000494:pharmacology*; D008264:Macrophages; D008666:Metalloendopeptidases / Q000037:antagonists & inhibitors*; D051379:Mice; D011480:Protease Inhibitors / Q000494:pharmacology*; D011485:Protein Binding; D013329:Structure-Activity Relationship
D000942:Antigens, Bacterial; D001427:Bacterial Toxins; D004791:Enzyme Inhibitors; D016859:Lipoxygenase Inhibitors; D011480:Protease Inhibitors; C030325:anthrax toxin; D004851:Epoxide Hydrolases; D008666:Metalloendopeptidases; C043134:leukotriene A4 hydrolase