Anthrax Lethal Factor: Difference between revisions

Anthrax Toxin, encoded by plasmid pXO2, is considered an AB toxin, with two A domains (EF and LF) and one B domain (PA). <ref name=Collier>PMID: 14570563</ref> <ref>Brenda A. Wilson, Abigail A. Salyers, Dixie D. Whitt, and Malcolm E. Winkler. Third Edition. Bacterial Pathogenesis A Molecular Approach</ref> On their own, these three domains are nontoxic, but any combination involving PA with EF and/or LF is what causes the physiological effects. <ref>Kenneth Todar, PhD. (2008). http://textbookofbacteriology.net/Anthrax_3.html</ref> Initially PA is a 83kDa protein which binds to the host Anthrax toxin Receptor (ATR). Upon binding, PA is cleaved into two fragments by furin proteases to become a 63 kDa protein bound to the ATR. Cleavage of PA allows self association to occur which forms a ring shaped heptamer know as the pore precursor (prepore). The prepore is now able to bind up to three molecules of EF and/or LF, leading to endocytosis of the complex. In the endosome, the prepore converts to a transmembrane pore, allowing translocation of EF and LF to the cytosol of target cell through a mechanism that is not well understood. EF and LF are now able to carry out their enzymatic activity on the host cell. <ref name=Collier>PMID: 14570563</ref>

Anthrax is primarily a disease of domesticated and wild animals. Herbivores such as cattle, sheep, horses, mules and goats are primarily affected because these animals maybe grazing on soils contaminated with ''Bacillus Anthracis'' endospores. <ref name=Collier>PMID: 14570563</ref> <ref>Kenneth Todar, PhD. (2008). http://textbookofbacteriology.net/Anthrax_3.html</ref> The blood of an animal that dies of anthrax can contain upward of 10^9 vegetative bacteria per milliliter and as the carcass decays, the bacteria form highly infectious endospores, which contaminate the local environment and can remain viable for long time periods. <ref name=Collier>PMID: 14570563</ref> The endosopres produced by ''Bacillus Anthracis'' remains viable for lengthy periods do to the poly-D-glutamic acid capsule, which itself is nontoxic. This capsule functions to protect the endospore  from complement and other bactericidal components found in serum. This capsule plays an important role during the infection of anthrax, but is not important during the disease phase, which is caused by PA, EF, LF. Genes encoding this plasmid are located on plasmid pXO2. <ref name=Collier>PMID: 14570563</ref> <ref>Kenneth Todar, PhD. (2008). http://textbookofbacteriology.net/Anthrax_3.html</ref> Anthrax is not a common disease among humans because it can not be transmittable from human to human. Humans become infected by being exposed to farm animals or contaminated animal products such as wool, hides, flesh and  blood. There are three ways in which Anthrax can be transmitted to humans: <ref name=Collier>PMID: 14570563</ref> <ref>Kenneth Todar, PhD. (2008). http://textbookofbacteriology.net/Anthrax_3.html</ref>

Antibiotics are used to treat Cutaneous and Inhalation Anthrax infections. The primary antibiotics used are Ciprofloxacin and Doxycycline. Antibiotics should to be administered before symptoms arise, which will likely decrease the fatality rate. In the case of inhalation, treat should be received with 24 hours. If administered after symptoms arise, there is a high rate of fatality. The duration of treatment is 60 days of antibiotics to ensure all spores have germinated. In some cases more than two antibiotics are administered. <ref>CDC. http://www.bt.cdc.gov/agent/anthrax/faq/treatment.asp</ref>.

'''<scene name='Anthrax_Lethal_Factor/Domain_-1-/1'>Domain I</scene>''' functions in the binding of Lethal Factor to Protective Antigen 63 (PA63), which is the membrane translocation component of Anthrax Toxin, but the actual location where domain I interacts with PA is unknown. <ref name=Collier>PMID: 14570563</ref> Domain I(residues 1-263) is perched above the other three domains and is connected to the rest of the domains through an abrupt turn at the end of the last helix.<ref name=Collier>PMID: 14570563</ref> Domain I consist of 12-helix bundle, packs against one face of a mixed four-stranded beta-sheet.<ref name=Collier>PMID: 14570563</ref> <ref name=Pannifer AD, Wong TY, Schwarzenbacher R, Renatus M, Petosa C, Bienkowska J, Lacy DB, Collier RJ, Park S, Leppla SH, Hanna P, Liddington RC>PMID: 11700563</ref>