Botulinum neurotoxin, tetanus toxin, and anthrax lethal factor countermeasures

Bioterrorism constitutes the deliberate release and dissemination of biological agents to incapacitate, maim, or kill individuals, groups, or populations, including humans, animals, and/or plants, in acts of terrorism. When carried out in the context of war, these acts are also termed biological warfare. Agents can be of bacterial, fungal, or plant origin; bacterial toxins are of particular concern as bioweapons due to their ease of production and weaponization, and their high level of toxicity to humans. Most macromolecular toxin-based biowarfare agents are metalloenzymes, featuring a catalytic metal in their active site(s) that is chiefly responsible for proteolytic activity leading to host cytotoxicity. This chapter outlines recent work on three metalloenzyme toxin types which exhibit high potential for deployment as bioterror agents: the botulinum neurotoxins (BoNTs), the tetanus toxin (TeNT, also known as tetanospasmin), and the anthrax toxin lethal factor (LF). All of these enzymes are deadly to humans; additionally, they are challenging to detect, and their toxic effects are difficult to treat. Although a great deal of research effort in this area has resulted in key steps forward that are discussed here, reliable and effective post-exposure countermeasures to these toxins remain elusive. A comprehensive national security and anti-bioterrorism strategy in the twenty-first century must therefore prioritize continuing research to combat these threats.