Medical Applications of Clostridia and Clostridial Toxins
1Integrated Toxicology Division, United States Army Medical Research Institute of Infectious Diseases, Fort Detrick, Frederick, MD 21702-5011, USA
2Biochemistry Department, University of Massachusetts, Dartmouth, Amherst, MA 01003, USA
Medical Applications of Clostridia and Clostridial Toxins
Description
Clostridia are anaerobic spore-forming bacteria found throughout the environment in various oxygen-free habitats. While the bacterial genus Clostridium contains over 100 species, approximately 20 are known to cause disease in humans and animals, with most pathologic effects caused by toxins or enzymes released by germinating spores. The diseases caused by Clostridia are as diverse as the toxins they produce and include botulism, gas gangrene, and antibiotic-associated diarrhea. The same characteristics that make Clostridia excellent pathogens have also made the Clostridia an abundant source for development of pharmacological agents. Perhaps the most well-known example type A Botulinum neurotoxin (BoNT/A) is produced by Clostridium botulinum and used to treat many conditions such as focal dystonias, spasticity, migraines, hemifacial spasms, and other conditions that do not respond to other pharmacological treatments. Although less well known, other clostridial toxins are being used or being studied for their applicability to treat collagen-associated diseases, wound debridement, and cancer. In addition to their protein toxins, the bacteria itself provide an excellent oncolytic agent in which nonpathogenic Clostridia are engineered to contain oncolytic genes. The anerobic clostridia seek the oxygen-reduced environment of the tumor and then release factors that kill the tumor cells.The ability to engineer clostridia or its toxins to target specific cells and tissues will lead to the development of new therapeutics that are specific and effective. The emphasis of this special issue will focus on the design of novel therapeutics based upon clostridia or clostridial toxins. Potential topics include, but are not limited to:
- Enzymatic (toxic) chain moieties that disrupt specific cellular events. An example would be the use of C. botulinum neurotoxin light chains to inhibit SNARE-mediated secretion
- Delivery vehicles that target drugs to specific cells or tissues. An example would be the use of clostridial neurotoxin heavy chains to target drugs to neuronal cells
- Toxin fragments to treat specific diseases and tissue damage. Examples include C. difficile toxin, a fragments to treat colon and pancreatic cancers
- Hypoxia-activated enzyme therapy. Examples include tumor therapeutics
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