Anthrax Toxin
Francisco J. Maldonado-Arocho, Kathleen M. Averette-Mirrashidi, and Kenneth A. Bradley
from: Microbial Toxins: Current Research and Future Trends (Edited by: Thomas Proft). Caister Academic Press, U.K. (2009)
Abstract
Bacillus anthracis produces two major virulence factors, a tripartite exotoxin referred to as anthrax toxin, and an antiphagocytic capsule. These virulence factors mediate pathogen survival and, in the case of toxin, directly induce damage to the host. Two distinct enzymatic activities are associated with anthrax toxin, each encoded by a separate protein. The enzymatic subunits are lethal factor (LF), a zinc-dependent metalloproteinase, and oedema factor (EF), a calcium- and calmodulin-dependent adenylate cyclase. (Leppla, 1982; 1984; Vitale et al., 1998; 1999). LF and EF gain access to the host cytosol by binding to and translocating through a pore formed by the shared binding subunit, protective antigen (PA) (Blaustein et al., 1989; Milne et al., 1994; Zhang et al., 2004a; 2004b). The combination of LF and PA is called lethal toxin (LT), and this toxin inactivates MAPK signaling in the host. Oedema toxin (ET), formed by the combination of EF and PA, produces high cAMP levels in host cells. Early during infection, systemic toxin levels are low, and likely modulate the host immune response locally, thereby allowing for establishment of infection. Late in infection, toxin concentrations increase causing organ damage, vascular leakage, and ultimately death of the host. Indeed, both LT and ET are capable of inducing mortality in animal models when injected as purified toxins. This chapter will focus on current trends in LT and ET research aimed at understanding the mechanisms by which they affect the host and alter disease outcome read more ...
