Abstract
Botulinum neurotoxins (BoNTs) rank amongst the most potent toxins known. The factors responsible for the emergence of the many known and yet unknown BoNT variants remain elusive. It also remains unclear why anaerobic bacteria that are widely distributed in our environment and normally do not pose a threat to humans, produce such deadly toxins. Even the possibility of accidental toxicity to humans has not been excluded. Here, I review the notion that BoNTs may have specifically evolved to target vertebrates. Considering the extremely complex molecular architecture of the toxins, which enables them to reach the bloodstream, to recognize and enter neurons, and to block neurotransmitter release, it seems highly unlikely that BoNT toxicity to vertebrates is a coincidence. The carcass–maggot cycle provides a plausible explanation for a natural role of the toxins: to enable mass reproduction of bacteria, spores, and toxins, using toxin-unaffected invertebrates, such as fly maggots, as the vectors. There is no clear correlation between toxigenicity and a selective advantage of clostridia in their natural habitat. Possibly, non-toxigenic strains profit from carcasses resulting from the action of toxigenic strains. Alternatively, a gene-centered view of toxin evolution would also explain this observation. Toxin-coding mobile genetic elements may have evolved as selfish genes, promoting their own propagation, similar to commensal viruses, using clostridia and other bacteria as the host. Research addressing the role of BoNTs in nature and the origin of toxin variability goes hand in hand with the identification of new toxin variants and the design of improved toxin variants for medical applications. These research directions may also reveal yet unknown natural antidotes against these extremely potent neurotoxins.
Highlights
Botulinum neurotoxins (BoNTs) rank amongst the most potent toxins known
The gene-centered view of toxin evolution described in this article provides a possible explanation for the observation that BoNT sequences appear to evolve, clostridia do not seem to gain a selective advantage from BoNT production
A serotype is defined in increased propagation the bacterial strain and of the toxin(BoNTs) as a toxinAt that can be neutralized with a type-specific antitoxin serotypes can further least seven serotypes (A–G) of botulinum neurotoxins (BoNTs) exist
Summary
Botulinum neurotoxins (BoNTs), produced and secreted by Clostridium botulinum and some other clostridia [1,2,3], rank amongst the most potent toxins known [4]. A serotype is defined in increased propagation the bacterial strain and of the toxin(BoNTs) gene cluster. Phylogenetic of botulinum neurotoxin serotypes and subtypes,depicting depictingthe thelarge largeindiversity in amino the toxin acid sequences. In an analysis of several thousand publically available metagenome datasets covering multiple environments, the largest number of DNA sequences with similarity to the catalytic domain of BoNTs were detected in samples from these bacterial habitats, and the study unveiled gene fragments with similarity to botulinum toxins in the metagenomes of insect guts [25]. As a result of recombination in the ntnh gene, the bont/A1 gene can be associated either with ha+ or orfX+ toxin clusters, an arrangement that has not been observed for any other subtype [40].
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
