Editing Anthrax (section)

== Mechanism ==
The lethality of the anthrax disease is due to the bacterium's two principal virulence factors: the [[polyglutamic acid|poly-D-glutamic acid capsule]], which protects the bacterium from phagocytosis by host neutrophils; and the tripartite protein toxin, called [[anthrax toxin]], consisting of protective [[antigen]] (PA), [[edema]] factor (EF), and lethal factor (LF).<ref name=toxin>{{cite web |url=http://www.ks.uiuc.edu/Research/anthrax/ |title=Molecular Basis for Anthrax Intoxication | vauthors = Gao M |date=27 April 2006 |publisher=University of Illinois at Urbana-Champaign |access-date=26 December 2016 |archive-url=https://web.archive.org/web/20161226202812/http://www.ks.uiuc.edu/Research/anthrax/ |archive-date=26 December 2016 |url-status=live}}</ref> PA plus LF produces lethal toxin, and PA plus EF produces edema toxin. These toxins cause death and tissue swelling ([[edema]]), respectively.
To enter the cells, the edema and lethal factors use another protein produced by ''B. anthracis'' called protective antigen, which binds to two surface receptors on the host cell. A cell [[protease]] then cleaves PA into two fragments: PA<sub>20</sub> and PA<sub>63</sub>. PA<sub>20</sub> dissociates into the extracellular medium, playing no further role in the toxic cycle. PA<sub>63</sub> then oligomerizes with six other PA<sub>63</sub> fragments forming a heptameric ring-shaped structure named a prepore. Once in this shape, the complex can competitively bind up to three EFs or LFs, forming a resistant complex.<ref name="Pimental04"/> Receptor-mediated endocytosis occurs next, providing the newly formed toxic complex access to the interior of the host cell. The acidified environment within the endosome triggers the heptamer to release the LF and/or EF into the cytosol.<ref>{{cite journal | vauthors = Chvyrkova I, Zhang XC, Terzyan S | title = Lethal factor of anthrax toxin binds monomeric form of protective antigen | journal = Biochemical and Biophysical Research Communications | volume = 360 | issue = 3 | pages = 690–95 | date = August 2007 | pmid = 17617379 | pmc = 1986636 | doi = 10.1016/j.bbrc.2007.06.124 }}</ref> It is unknown how exactly the complex results in the death of the cell.

Edema factor is a [[calmodulin]]-dependent [[adenylate cyclase]]. Adenylate cyclase catalyzes the conversion of ATP into [[cyclic AMP]] (cAMP) and [[pyrophosphate]]. The complexation of adenylate cyclase with [[calmodulin]] removes calmodulin from stimulating calcium-triggered signaling, thus inhibiting the immune response.<ref name="Pimental04"/> To be specific, LF inactivates [[neutrophil]]s (a type of phagocytic cell) by the process just described so they cannot phagocytose bacteria. Throughout history, lethal factor was presumed to cause macrophages to make [[TNF-alpha]] and [[IL1B|interleukin 1 beta]] (IL1B). TNF-alpha is a [[cytokine]] whose primary role is to regulate immune cells, as well as to induce inflammation and [[apoptosis]] or programmed cell death. Interleukin 1 beta is another cytokine that also regulates inflammation and apoptosis. The overproduction of TNF-alpha and IL1B ultimately leads to [[septic shock]] and death. However, recent evidence indicates anthrax also targets endothelial cells that line serious cavities such as the [[pericardial cavity]], [[pleural cavity]], and [[peritoneal cavity]], lymph vessels, and blood vessels, causing vascular leakage of fluid and cells, and ultimately [[hypovolemic shock]] and septic shock.{{citation needed|date=May 2021}}