Bacillus Anthracis: Anthrax Lethal Toxin: Difference between revisions
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==Anthrax Toxin Neutralization with Antibody== | ==Anthrax Toxin Neutralization with Antibody== | ||
<p>During infection by B. anthracis, protective antigen is integral in the intoxication of the host cells by anthrax toxins. This protein, therefore, is a logical target for scientists seeking to neutralize the anthrax toxins. Mechaly, et al. have recently found that the antibody cAb29, does just that: it targets PA molecules, interfering with the function of the molecule and thereby neutralizing the anthrax toxin (Mechaly).[[Image:cAb29Fig.jpg|thumb|300px|center|Figure 1. A and B show the neutralization assay performed using cultured J774A macrophages that were incubated for 5 h with fixed amounts of LF and PA83 (A) or purified prepore (B) in the presence of cAb29 (circles) or Ab33 (triangles) in the indicated concentrations. Cell survival was determined by XTT and plotted as the percentage of untreated control cells. Points are mean ± S.D. of triplicate determinants. Ab concentration, antibody concentration (Mechaly).]]</p> | |||
<p>The Mechaly group, in attempting to determine the mechanism by which cAb29 functions to neutralize the toxins, found that cAb29 does not have any effect on the initial steps of the intoxication process: PA molecules are still able to bind to the target cell via receptors on the target cell membrane. These molecules are still cleaved by the furin-family protease and they still oligomerize into hepatomers which bind EF and LF molecules. Instead, they discovered that the antibody binds to the prepore, which is the complex of PA and either LF or EF before it is internalized by the cell, preventing the acid catalyzed transition to the transmembranal pore (Mechaly). </p> | |||
<p>Their tests showed 100% survival of mice injected intravenously with cAb29 12 hours after initial exposure to B. anthracis (Figure 1). This is a very important discovery as it could possibly lead to a cure for the disease even if it is not caught in the very early stages of infection (Mechaly).</p> | |||
[[Image:cAb29Fig.jpg|thumb|300px|center|Figure 1. A and B show the neutralization assay performed using cultured J774A macrophages that were incubated for 5 h with fixed amounts of LF and PA83 (A) or purified prepore (B) in the presence of cAb29 (circles) or Ab33 (triangles) in the indicated concentrations. Cell survival was determined by XTT and plotted as the percentage of untreated control cells. Points are mean ± S.D. of triplicate determinants. Ab concentration, antibody concentration (Mechaly).]] | |||
==Target Cells in Humans in Inhalation Anthrax== | ==Target Cells in Humans in Inhalation Anthrax== |
Revision as of 02:26, 25 April 2013
Introduction
By Connor Gibbons
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Anthrax is a disease that typically affects herbivores but can infect any mammal, including humans. It is caused by the bacterium Bacillus anthracis (B. anthracis). This disease has become a hot topic in today’s society, in which terrorism is becoming more prevalent, as it can be used in biological warfare. Recently, there has also been an increase in the number of cases of injection anthrax, a form of the disease that affects heroin users, in Europe (Grunow). However, this disease is not new. In fact, there is evidence of it throughout history. The fifth and sixth plagues in Egypt (Exodus, Chapter 9) have been attributed to this pathogen (Baillie).
The species derives its name from the Greek word anthrakis, meaning coal, because infection by the organism causes the formation of black, cutaneous eschars (Spencer). There are are three types of B. anthracis infection that are typically described: cutaneous anthrax (the cause of the black sores), inhalation anthrax (the most deadly form), and gastrointestinal anthrax (Mock, Mignot).
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Anthrax Toxin Neutralization with Antibody
During infection by B. anthracis, protective antigen is integral in the intoxication of the host cells by anthrax toxins. This protein, therefore, is a logical target for scientists seeking to neutralize the anthrax toxins. Mechaly, et al. have recently found that the antibody cAb29, does just that: it targets PA molecules, interfering with the function of the molecule and thereby neutralizing the anthrax toxin (Mechaly).
The Mechaly group, in attempting to determine the mechanism by which cAb29 functions to neutralize the toxins, found that cAb29 does not have any effect on the initial steps of the intoxication process: PA molecules are still able to bind to the target cell via receptors on the target cell membrane. These molecules are still cleaved by the furin-family protease and they still oligomerize into hepatomers which bind EF and LF molecules. Instead, they discovered that the antibody binds to the prepore, which is the complex of PA and either LF or EF before it is internalized by the cell, preventing the acid catalyzed transition to the transmembranal pore (Mechaly).
Their tests showed 100% survival of mice injected intravenously with cAb29 12 hours after initial exposure to B. anthracis (Figure 1). This is a very important discovery as it could possibly lead to a cure for the disease even if it is not caught in the very early stages of infection (Mechaly).
Target Cells in Humans in Inhalation Anthrax
References
Edited by student of Joan Slonczewski for BIOL 238 Microbiology, 2011, Kenyon College.