J. Clin. Invest. 109: 141–144 (2002). doi: 10.1172/JCI200216204. administration of anthrax toxin to monkeys, anthrax can be considered a toxin-mediated disease. The virulence of B. anthracis results from the action of materials that are expressed from genes on two large plasmids, pX01 and pX02 (12, 13). pX01 encodes the proteins that make up the anthrax toxin. The massive edema and organ failure seen in anthrax patients are caused largely by the action of three individually nontoxic proteins: protective antigen (PA, 83 kDa), edema factor (EF, adenylate cyclase, 89 kDa), and lethal factor (LF, zinc protease, 90 kDa)(14). The latter two combine with the PA to form edema toxin and lethal toxin, respectively. PA, EF, and LF fit the AB toxin model proposed by Gill (15). Thus, following its interaction with host cells, PA (the “B” subunit) is activated by the cellular protease furin, causing the release of a 20-kDa N-terminal domain (16). The remaining 63-kDa polypeptide creates a heptameric structure that constitutes a channel in the host cell membrane (17) through which LF and EF (each of which represents an alternative “A” subunit in this model) are translocated to the cytosol. The unregulated adenylate cyclase activity of EF leads to production of unphysiologically high concentrations of cAMP, one consequence of which is incapacitation of phagocytic cells (14). LF cleaves several mitogen-activated protein kinase kinases, thereby blocking signal transduction pathways by which host immune cells normally respond to pathogens (18, 19). Plasmid pX02 encodes the poly-γ-linked D-glutamic acid (PGA) capsule, demonstrable by a Quellung (antibody-induced swelling) reaction (20). Strains lacking pX02 are avirulent. PGA confers virulence to