A new source of the botulinum neurotoxin was discovered by Canadian and American scientists in a strain of animal gut bacteria known as Enterococcus faecium. The neurotoxic protein is known for its paradoxical ability to remove wrinkles yet cause botulism, a potentially fatal illness associated with food poisoning.
Over the past 20 years, there has also been a growing number of therapeutic applications for botulinum toxin type A, known as Botox, including treatment for migraines, leaky bladders, excessive sweating, and cardiac conditions.
"This is the first time that an active botulinum toxin has been identified outside of Clostridium botulinum and its relatives, which are often found in soil and untreated water," said one of the study's two corresponding authors. "Its discovery has implications in several fields, from monitoring the emergence of new pathogens to the development of new protein therapeutics--it's a game changer."
In the study, originally designed to investigate the origins of antibiotic resistance in E. faecium bacteria, the researchers were able to sequence the genome of the E. faecium bacteria drawn from cow feces. The genome was then run through computer programs, which found the gene for botulinum toxin in the bacterial strain.
It cleaves both VAMP2 and SNAP-25, proteins that mediate synaptic vesicle exocytosis in neurons, at sites distinct from known BoNT cleavage sites on these two proteins. Comparative genomic analysis determines that the E. faecium strain carrying BoNT/En is a commensal type and that the BoNT/En gene is located within a typical BoNT gene cluster on a 206 kb putatively conjugative plasmid.
The researchers concluded that the botulinum toxin was likely transferred from C. botulinum bacteria in the environment into the E. faecium bacteria in the cow's gut, showing that the toxin can be transferred between very different species.
"The botulinum toxin is a powerful and versatile protein therapeutic" says one of the study's lead authors. "By finding more versions of the toxin in nature, we can potentially expand and optimize its therapeutic applications even further."