Anthrax Toxin Chronicles: Celebrating 70 Years of Scientific Breakthroughs in Chemistry, Biology, and Toxicology
A special issue of Toxins (ISSN 2072-6651). This special issue belongs to the section "Bacterial Toxins".
Deadline for manuscript submissions: 1 October 2025 | Viewed by 3588
Special Issue Editor
Special Issue Information
Dear Colleagues,
The lethal effects of Bacillus anthracis, the causative agent of anthrax, are primarily due to the ability of the bacilli to synthesize and secrete a tripartite exotoxin comprising lethal factor (LF), calmodulin-activated edema factor (EF), and protective antigen (PA), encoded by the pX01 plasmid. LF and EF each combine with PA to form the lethal toxin and edema toxin, respectively, both of which enter cells via a PA-mediated, furin-like endocytosis mechanism. Once inside host cells, LF interferes with cellular immune host defense mechanisms against microbial pathogens and causes disruption of vascular barriers, directly leading to hypovolemia and host death. Inhalational anthrax can be particularly challenging to treat due to nonspecific initial disease symptoms and rapid toxin secretion by vegetative bacteria. Weaponized B. anthracis spores have been deployed as a bioterror weapon, and anthrax continues to pose a global threat to military and civilian populations. However, much progress has been made in the 70 years since anthrax toxins were first identified. Multidisciplinary and interdisciplinary research has yielded breakthroughs in anthrax structural biology, enzymology, and pre- and post-exposure therapeutic design. For example, the lethal factor has garnered a great deal of research attention as a therapeutic target, with several apo- and complexed crystal structures deposited in the Protein Data Bank and multiple inhibitor series reported in the literature. Advances in monoclonal antibody-based treatments and vaccine development targeting PA have been remarkable, with novel emergency antidotes now deployable as part of the U.S. Strategic National Stockpile. Researchers now have an improved understanding of anthrax toxin mechanisms and are investigating their use as potential therapeutic vehicles capable of targeting tumors. Still, key questions remain, including the multiplicity of toxin targets and the feasibility of small-molecule LF-inhibitor antitoxins, among others. This Special Issue will showcase major scientific breakthroughs in anthrax toxin research achieved over the last seven decades and will feature results spanning multiple disciplines, including medicinal chemistry, biochemistry, microbiology, toxicology, and immunology. This Special Issue will also include reports of ongoing research in antitoxin development and the use of anthrax toxins in “nonstandard” applications such as drug delivery, as well as assessments of future research directions and priorities.
Dr. Elizabeth A. Ambrose
Guest Editor
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Keywords
- anthrax
- Bacillus anthracis
- lethal factor
- bioterrorism
- antitoxins
- zinc metalloprotease
- edema factor
- protective antigen
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