Bacillus anthracis is the etiological agent of anthrax

Major virulence factors produced by Bacillus anthracis are the gamma-linked, poly-D-glutamic acid capsule and an exotoxin composed of three components, protective antigen (PA), lethal factor (LF), and edema factor (EF). These proteins are not toxic separately but act in binary combinations. The complex of PA, the cell binding component, with LF, one of the enzymatic moieties, is termed "lethal toxin" and can cause death. PA and the enzymatic EF together cause skin edema. After secretion, PA is cleaved by membrane peptidases, allowing the 63 kDa carboxy terminal fragment to oligomerize to a heptamer. Cleavage is an essential step in exposing the binding sites for EF and LF. The assembled PA complex and associated LF or EF enters the cell through endocytosis. PA mediates the transfer of LF and EF to the cytoplasm where these enzymes recognize and proteolyze their targets. The LF component, a zinc-dependent metalloprotease, cleaves the mitogen-activated protein kinase kinase (MAPKK), impairing its function and thereby blocking the MAPK signaling pathway. EF is a calmodulin-dependent adenylate cyclase which creates in the cell excess amounts of cyclic-AMP, resulting in edema. Current research is focused on the development of an effective vaccine as well as screening for potent inhibitors of the LF enzymatic activity.