C. perfringens iota toxin and C. botulinum C2 toxin, attach a ribosyl-ADP moiety to surface arginine residue 177 of G-actin. This prevents G-actin assembling to form F-actin, and, thus, the cytoskeleton breaks down, resulting in cell death. Insecticidal members of the ADP-ribosyltransferase family of toxins include the Mtx1 toxin of Lysinibacillus sphaericus and the Vip1/Vip2 toxin of Bacillus thuringiensis and some members of the toxin complex (Tc) toxins from gram negative bacteria such as Photorhabdus and Xenorhabdus species. The beta sheet-rich regions of the Mtx1 protein are lectin-like sequences that may be involved in glycolipid interactions. Proteolysis of mitogen-activated protein kinase kinases (MAPKK) The A component of anthrax toxin lethal toxin is zinc-metalloprotease, which shows specificity for a conserved family of mitogen-activated protein kinases. The loss of these proteins results in a breakdown of cell signaling, which, in turn, renders the cell insensitive to outside stimuli – therefore no immune response is triggered. Increasing intracellular levels of cAMP Anthrax toxin edema toxin triggers a calcium ion influx into the target cell. This subsequently elevates intracellular cAMP levels. This can profoundly alter any sort of immune response, by inhibiting leucocyte proliferation, phagocytosis, and proinflammatory cytokine release. Cholesterol-dependent cytolysins CDCs, such as pneumolysin, from S. pneumoniae, form pores as large as 260Å (26 nm), containing between 30 and 44 monomer units. Electron microscopy studies of pneumolysin show that it assembles into large multimeric peripheral membrane complexes before undergoing a conformational change in which a group of α-helices in each monomer change into extended, amphipathic β-hairpins that span the membrane, in a manner reminiscent of α-haemolysin, albeit on a much larger scale (Fig 3). CDCs are homologous to the MACPF family of pore-forming toxins, and it is suggested that both families use a common mechanism (Fig 4). Eukaryote MACPF proteins function in immune defence and are found in proteins such as perforin and complement C9 though perivitellin-2 is a MACPF attached to a delivery lectin that has enterotoxic and neurotoxic properties toward mice. A family of highly conserved cholesterol-dependent cytolysins, closely related to perfringolysin from Clostridium perfringens are produced by bacteria from across the order Bacillales and include anthrolysin, alveolysin and sphaericolysin. Sphaericolysin has been shown to exhibit toxicity to a limited range of insects injected with the purified protein. Biological function Bacteria may invest much time and energy in making these toxins: CPE can account for up to 15% of the dry