» Articles » PMID: 8973585

The Cytotoxic Activity of Bacillus Anthracis Lethal Factor is Inhibited by Leukotriene A4 Hydrolase and Metallopeptidase Inhibitors

Overview
Journal Biochem J
Specialty Biochemistry
Date 1996 Dec 1
PMID 8973585
Citations 6
Authors
Affiliations
Soon will be listed here.
Abstract

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.

Citing Articles

Profiling lethal factor interacting proteins from human stomach using T7 phage display screening.

Cardona-Correa A, Rios-Velazquez C Mol Med Rep. 2016; 13(5):3797-804.

PMID: 27035230 PMC: 4838128. DOI: 10.3892/mmr.2016.5031.


Designed azolopyridinium salts block protective antigen pores in vitro and protect cells from anthrax toxin.

Beitzinger C, Bronnhuber A, Duscha K, Riedl Z, Huber-Lang M, Benz R PLoS One. 2013; 8(6):e66099.

PMID: 23840407 PMC: 3688708. DOI: 10.1371/journal.pone.0066099.


High-affinity, human antibody-like antibody fragment (single-chain variable fragment) neutralizing the lethal factor (LF) of Bacillus anthracis by inhibiting protective antigen-LF complex formation.

Pelat T, Hust M, Laffly E, Condemine F, Bottex C, Vidal D Antimicrob Agents Chemother. 2007; 51(8):2758-64.

PMID: 17517846 PMC: 1932538. DOI: 10.1128/AAC.01528-06.


Binary bacterial toxins: biochemistry, biology, and applications of common Clostridium and Bacillus proteins.

Barth H, Aktories K, Popoff M, Stiles B Microbiol Mol Biol Rev. 2004; 68(3):373-402, table of contents.

PMID: 15353562 PMC: 515256. DOI: 10.1128/MMBR.68.3.373-402.2004.


Susceptibility of mitogen-activated protein kinase kinase family members to proteolysis by anthrax lethal factor.

Vitale G, Bernardi L, Napolitani G, Mock M, Montecucco C Biochem J. 2000; 352 Pt 3:739-45.

PMID: 11104681 PMC: 1221512.


References
1.
Wallace J, Macnaughton W, Morris G, Beck P . Inhibition of leukotriene synthesis markedly accelerates healing in a rat model of inflammatory bowel disease. Gastroenterology. 1989; 96(1):29-36. DOI: 10.1016/0016-5085(89)90760-9. View

2.
Lecomte J, Costentin J, Vlaiculescu A, Chaillet P, Llorens-Cortes C, Leboyer M . Pharmacological properties of acetorphan, a parenterally active "enkephalinase" inhibitor. J Pharmacol Exp Ther. 1986; 237(3):937-44. View

3.
Hansen M, Nielsen S, Berg K . Re-examination and further development of a precise and rapid dye method for measuring cell growth/cell kill. J Immunol Methods. 1989; 119(2):203-10. DOI: 10.1016/0022-1759(89)90397-9. View

4.
Gillard J, Ford-Hutchinson A, Chan C, Charleson S, Denis D, Foster A . L-663,536 (MK-886) (3-[1-(4-chlorobenzyl)-3-t-butyl-thio-5-isopropylindol-2-yl]-2,2 - dimethylpropanoic acid), a novel, orally active leukotriene biosynthesis inhibitor. Can J Physiol Pharmacol. 1989; 67(5):456-64. DOI: 10.1139/y89-073. View

5.
Samuelsson B, Funk C . Enzymes involved in the biosynthesis of leukotriene B4. J Biol Chem. 1989; 264(33):19469-72. View