Bacillus anthracis bacteria target cells in an infected human through the action of three secreted bacterial proteins, LF, EF, and PA (reviews: Turk 2007; Young and Collier 2007). LF (lethal factor) is a protease that cleaves and inactivates many MAP2K (MAP kinase kinase, MEK) proteins (Duesbery et al. 1998; Vitale et al. 2000), disrupting MAP kinase signaling pathways. EF (edema factor) is an adenylate cyclase that mediates the constitutive production of cAMP (Leppla 1982), a molecule normally generated transiently in tightly regulated amounts in response to extracellular signals. Both LF and EF depend on PA (protective antigen) to enter their target cells, a strategy characteristic of bacterial binary toxins (Barth et al. 2004). PA binds to the target cell receptors, is cleaved by furin or other cellular proteases, and thereupon forms an oligomer that exposes binding sites for LF and EF molecules (review: Young and Collier 2007). This complex is taken into the target cell by clathrin mediated endocytosis and delivered to endosomes. The low pH of the endosome causes the bacterial toxin complex to rearrange: the PA oligomer forms a pore in the endosome membrane through which EF and LF molecules enter the target cell cytosol.
Vande Woude, GF