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Prior to the extraordinary interest in generated by the recent bioterrorism events in the United States, much of microbiologists' awareness of the bacterium resulted from its historical significance. can infect all mammals, some birds, and possibly even reptiles. Systemic anthrax, generally resulting from inhalation or ingestion of spores, has a high fatality rate. is a facultative anaerobe and grows in most rich undefined media with a doubling time of approximately 30 min. Experimental studies of anthrax toxin are summarized in this chapter. The majority of animal models for anthrax have been used to assess pathophysiological effects of purified toxin and to test efficacy of vaccines against anthrax. When is grown under appropriate conditions, the outermost surface of vegetative cells is covered by a capsule. As is true for numerous pathogens, the capsule is an important virulence factor. Toxin and capsule synthesis by represents an intriguing example of coordinate expression of virulence genes in response to host-related cues. Major advances in understanding of structure and function of the "classic" virulence factors of , the anthrax toxin proteins and the poly-D-glutamic capsule, combined with new information regarding the anthrax toxin receptors are fueling new strategies for anthrax therapeutics and improved human vaccines. Molecular genetic analyses involving multiple strains will continue to facilitate epidemiological studies and development of advanced methods for detection and identification.

Citation: Koehler T. 2006. , p 659-671. In Fischetti V, Novick R, Ferretti J, Portnoy D, Rood J (ed), Gram-Positive Pathogens, Second Edition. ASM Press, Washington, DC. doi: 10.1128/9781555816513.ch54

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Live Attenuated Bacterial Vaccines
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( Ribbon diagrams representing structures of the anthrax toxin proteins. (A) Monomeric PA. Ia (blue), 20-kDa fragment removed with cleavage; Ib (yellow), forms N terminus of PA and contains two structural calcium ions (red); II (green), pore formation; III (magenta), oligomerization of PA; IV (turquoise), receptor binding. (B) LF. Substrate-binding and catalytic domains (green) and PA-binding domain (magenta). (C) EF in complex with calmodulin. Catalytic core (green); PA-binding domain (magenta); helical domain (yellow) interacts with calmodulin (red). (Courtesy of W.-J. Tang.)

Citation: Koehler T. 2006. , p 659-671. In Fischetti V, Novick R, Ferretti J, Portnoy D, Rood J (ed), Gram-Positive Pathogens, Second Edition. ASM Press, Washington, DC. doi: 10.1128/9781555816513.ch54
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Image of FIGURE 2

Model of anthrax toxin action. PA binds to receptors TEM8 or CMG2. Following proteolytic cleavage of PA by furin, PA oligomerizes to form a heptameric prepore. EF-LF binds to the prepore, and the complex is endocytosed. Acidification of the intracellular compartment triggers translocation of EF and LF to the cytosol. EF, a calmodulin-dependent adenylate cyclase, converts ATP to cAMP. LF, a zinc-dependent protease, cleaves members of the MEK family and may also affect other targets. (Reprinted from Moayeri and Leppla [ ].)

Citation: Koehler T. 2006. , p 659-671. In Fischetti V, Novick R, Ferretti J, Portnoy D, Rood J (ed), Gram-Positive Pathogens, Second Edition. ASM Press, Washington, DC. doi: 10.1128/9781555816513.ch54
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Image of FIGURE 3

Model depicting virulence gene regulation.

Citation: Koehler T. 2006. , p 659-671. In Fischetti V, Novick R, Ferretti J, Portnoy D, Rood J (ed), Gram-Positive Pathogens, Second Edition. ASM Press, Washington, DC. doi: 10.1128/9781555816513.ch54
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