Next Article in Journal / Special Issue
Botulinum Neurotoxin F Subtypes Cleaving the VAMP-2 Q58–K59 Peptide Bond Exhibit Unique Catalytic Properties and Substrate Specificities
Previous Article in Journal
Integrating Engineering, Manufacturing, and Regulatory Considerations in the Development of Novel Antivenoms
Previous Article in Special Issue
Engineering Botulinum Toxins to Improve and Expand Targeting and SNARE Cleavage Activity
Article Menu
Issue 8 (August) cover image

Export Article

Open AccessOpinion
Toxins 2018, 10(8), 310; https://doi.org/10.3390/toxins10080310

Botulinum Neurotoxin Diversity from a Gene-Centered View

Laboratory of Biomolecular Research, Division of Biology and Chemistry, Paul Scherrer Institute, Villigen CH-5232, Switzerland
Received: 13 June 2018 / Revised: 24 July 2018 / Accepted: 30 July 2018 / Published: 1 August 2018
(This article belongs to the Special Issue Novel BoNTs and Toxin Engineering)
Full-Text   |   PDF [1269 KB, uploaded 1 August 2018]   |  

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. View Full-Text
Keywords: botulinum neurotoxin evolution; toxin diversity; selfish genes; gene-centered view; the role of botulinum neurotoxins in nature; carcass–maggot cycle; toxin architecture botulinum neurotoxin evolution; toxin diversity; selfish genes; gene-centered view; the role of botulinum neurotoxins in nature; carcass–maggot cycle; toxin architecture
Figures

Figure 1

This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited (CC BY 4.0).
SciFeed

Share & Cite This Article

MDPI and ACS Style

Benoit, R.M. Botulinum Neurotoxin Diversity from a Gene-Centered View. Toxins 2018, 10, 310.

Show more citation formats Show less citations formats

Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Related Articles

Article Metrics

Article Access Statistics

1

Comments

[Return to top]
Toxins EISSN 2072-6651 Published by MDPI AG, Basel, Switzerland RSS E-Mail Table of Contents Alert
Back to Top