Uptake and function of anthrax toxins

Stable Identifier
R-HSA-5210891
Type
Pathway
Species
Homo sapiens
Related Species
Bacillus anthracis
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Bacillus anthracis bacteria target cells in an infected human through the action of three secreted bacterial proteins, lef (also known as LF, lethal factor), cya (also known as EF, edema factor), and pagA (also known as PA, protective antigen) (Turk 2007; Young and Collier 2007). lef is a protease that cleaves and inactivates many MAP2K (MAP kinase kinase, MEK) proteins (Duesbery et al. 1998; Vitale et al. 2000), disrupting MAP kinase signaling pathways. cya is an adenylate cyclase that mediates the constitutive production of cAMP (Leppla 1982), a molecule normally generated transiently in tightly regulated amounts in response to extracellular signals. Both lef and cya depend on pagA to enter their target cells, a strategy characteristic of bacterial binary toxins (Barth et al. 2004). pagA binds to the target cell receptors, is cleaved by furin or other cellular proteases, and thereupon forms an oligomer that exposes binding sites for lef and cya molecules (Young and Collier 2007). This complex is taken into the target cell by clathrin mediated endocytosis and delivered to endosomes. The low pH of the endosome causes the bacterial toxin complex to rearrange: the pagA oligomer forms a pore in the endosome membrane through which lef and cya molecules enter the target cell cytosol.

Literature References
PubMed ID Title Journal Year
9563949 Proteolytic inactivation of MAP-kinase-kinase by anthrax lethal factor

Duesbery, NS, Webb, CP, Leppla, SH, Gordon, VM, Klimpel, KR, Copeland, TD, Ahn, NG, Oskarsson, MK, Fukasawa, K, Paull, KD, Vande Woude, GF

Science 1998
17335404 Anthrax toxin: receptor binding, internalization, pore formation, and translocation

Young, JA, Collier, RJ

Annu. Rev. Biochem. 2007
11104681 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
15353562 Binary bacterial toxins: biochemistry, biology, and applications of common Clostridium and Bacillus proteins

Barth, H, Aktories, K, Popoff, MR, Stiles, BG

Microbiol. Mol. Biol. Rev. 2004
6285339 Anthrax toxin edema factor: a bacterial adenylate cyclase that increases cyclic AMP concentrations of eukaryotic cells

Leppla, SH

Proc. Natl. Acad. Sci. U.S.A. 1982
17313374 Manipulation of host signalling pathways by anthrax toxins

Turk, BE

Biochem. J. 2007
Participants
Participates
Disease
Name Identifier Synonyms
anthrax disease DOID:7427
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