Bacillus anthracis (BA) is an animal and human pathogen whose virulence is determined by lethal toxin, edema toxin, and a poly-glutamic acid capsule. We have recently described and begun to characterize a new putative BA toxin of the cholesterol-dependent cytolysin family, which we have named Anthrolysin O (ALO). We have shown that recombinant ALO (rALO) or native ALO secreted by BA is lethal to human primary polymorphonuclear cells (PMN), monocytes, monocyte-derived macrophages, and the THP-1 monocytic human cell line in a dose- and time-dependent manner.

We have also shown that rALO and native ALO, at sublethal concentrations, induce mouse bone marrow-derived macrophages to synthesize a pattern of cytokines that mimics that of lipopolysaccharide, suggesting that TLR4 is an ALO receptor. rALO induces mouse bone marrow-derived macrophages and the mouse macrophage-like cell line RAW 264.7 to phosphorylate p38. Studies are underway to examine ALO's role in human cell activation, interactions with the other toxins, and its role at the macrophage/bacteria interface.