On Botulinum Neurotoxin Variability

ABSTRACT The rapidly growing number of botulinum neurotoxin sequences poses the problem of the possible evolutionary significance of the variability of these superpotent neurotoxins for toxin-producing Clostridium species. To progress in the un-derstanding of this remarkable phenomenon, we suggest that researchers should (i) abandon an anthropocentric view of these neurotoxins as human botulism-causing agents or as human therapeutics, (ii) begin to investigate in depth the role of botulinum neurotoxins in animal botulism in the wilderness, and (iii) devote large efforts to next-generation sequencing of soil samples to identify novel botulinum neurotoxins. In order to compare the fitness of the different toxins, we suggest that assays of all the steps from toxin production to animal death should be performed. An intrinsic aspect of science in general and of experimentalsciences in particular is that a field or domain can remain unchanged or stagnant for many years. Then, it may change rap-idly, following the introduction of a novel paradigm or, more frequently, a technical innovation (1). This has recently happened for the botulinum neurotoxins (BoNTs), whose number rose rap-idly from a few BoNTs to several dozens in a few years, and many more are expected to be reported soon. These neurotoxins are the most potent bacterial toxins yet known; therefore, they are classi