Abstract
Bacillus anthracis is the causative agent of anthrax, a disease of animals that is transmissible to humans. Because B. anthracis forms spores that can be aerosolized and sprayed with the intent to kill, this pathogen can also be viewed as an agent of biological warfare and bioterrorism (1). The accidental release of spores into the air in Sverdlosk, Russia, and the recent mail attacks in the United States in the Fall of 2001 led to human casualties that sadly document the pathogenic potential and bioterrorism threat of B. anthracis (2,3). Furthermore, it appears that B. anthracis has been a research focus of biological warfare industries and subject to genetic manipulation with the intent of generating pathogen variants with increased virulence or with resistance to medical therapies and vaccine prevention strategies (1,4,5). B. anthracis can be obtained from infected animals or soil and anthrax spores are easily prepared. Furthermore, B. anthracis spores display very low visibility when delivered as an aerosol spray or powder. Inhalational anthrax is the primary target disease of biological warfare schemes (6). The LD50 for human inhalation of anthrax is not known, but has been estimated from animal studies to be of the order of 10,000 spores, corresponding to approx 0.01 µg (2,7), and a kilogram amount of spores, if sprayed intentionally on an urban area, is capable of killing hundreds of thousands of people. Biological warfare is an evolving research enterprise, and B. anthracis strains resistant to the commonly used antibiotic therapies may be available to several countries and terrorist organizations (6). American defense strategies against bioterrorist or biological warfare attacks must focus on the development of novel therapies that circumvent drug and vaccine-resistant B. anthracis strains (8). Much attention is directed toward finding inhibitors that disrupt the function of anthrax toxin. Anthrax toxin is the major virulence factor of B. anthracis (9) and consists of three proteins: lethal factor (LF), edema factor (EF), and protective antigen (PA). PA combines with either LF or EF enzymes to mediate their translocation across the plasma membrane (10). The combination of PA and LF forms lethal toxin (LeTx) and that of PA and EF forms edema toxin (EdTx). Once bacteria have secreted a large amount of anthrax toxin, antibiotic treatment becomes far less effective. At this later stage of anthrax pathogenesis, it might be useful to disrupt the biological activity of the toxin. This chapter reviews current knowledge of the factors that contribute to the pathogenesis of B. anthracis and highlights recent reports of possible strategies for blocking toxin action (11–13). Additionally, based on the known mechanisms of listeria-mediated invasion and virulence, the currently available genome sequences of B. anthracis were searched in an attempt to identify B. anthracis genes that may act early during pathogenesis by contributing to bacterial attachment to host tissues or to toxin secretion
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Missiakas, D.M., Schneewind, O. (2005). Bacillus anthracis and the Pathogenesis of Anthrax. In: Lindler, L.E., Lebeda, F.J., Korch, G.W. (eds) Biological Weapons Defense. Infectious Disease. Humana Press. https://doi.org/10.1385/1-59259-764-5:079
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