Botulinum Neurotoxins (BoNTs) and Their Biological, Pharmacological, and Toxicological Issues: A Scoping Review

Massimo Corsalini,Felice Lorusso,Ioannis Alexandros Charitos,Alessio Danilo Inchingolo,Francesco Inchingolo,Maria Assunta Potenza,Luigi Santacroce,Angelika Elzbieta Wegierska,Monica Montagnani,Gianna Dipalma,Antonio Scarano

doi:10.3390/app11198849

Abstract

Botulinum toxins or neurotoxins (BoNTs) are the most potent neurotoxins known, and are currently extensively studied, not only for their potential lethality, but also for their possible therapeutic and cosmetic uses. Currently, seven types of antigenically distinct toxins are known and characterized, produced by a rod-shaped bacterium, Clostridium botulinum. Human poisoning by botulism (presenting with severe neuromuscular paralytic disease) is usually caused by toxins A, B, E, and F type. Poisoning from contaminated food preparations is the most common cause of noniatrogenic botulism. The spores are highly resistant to heat but are easily destroyed at 80 °C for thirty minutes. Type A and B toxins are resistant to digestion by the enzymes of the gastrointestinal system. After their entry, BoNTs irreversibly bind to cholinergic nerve endings and block the release of acetylcholine from the synapses. In contrast, in wound botulism, the neurotoxin is instead product by the growth of C. botulium in infected tissues. The contamination by BoNT inhalation does not occur by a natural route but it is certainly the most dangerous. It can be caused by the dispersion of the botulinum toxin in the atmosphere in the form of an aerosol and therefore can be deliberately used for bioterrorist purposes (e.g., during CBRN (chemical, biological, radiological, and nuclear) unconventional events). In addition, BoNTs are currently used to treat a variety of diseases or alleviate their symptoms, such as the onabotulinumtoxinA for migraine attacks and for cosmetic use. Indeed, this paper aims to report on updated knowledge of BoNTs, both their toxicological mechanisms and their pharmacological action.

Highlights

The Clostridium genus, a part of the phylum Firmicutes, belongs to the family Clostridiaceae, class Clostridiales, prokaryotic microorganisms and is sporogenic, Gram (+) bacteria, and anaerobic
The toxin is released during bacterial cell lysis and each strain of C. botulinum usually produces only one type
The Botulinum toxins or neurotoxins (BoNTs) produced by C. botulinum are of a protein nature targeting the nervous system (Neurotoxic)

Summary

Introduction

The Clostridium genus, a part of the phylum Firmicutes, belongs to the family Clostridiaceae, class Clostridiales, prokaryotic microorganisms and is sporogenic, Gram (+) bacteria, and anaerobic (even if some species can live in the microaerophilic environment such as C.tertium and C. histolyticum). Some species are primarily pathogenic to humans, many are potentially pathogenic, and many other species are saprophytic. It is the largest and most heterogeneous genus of bacteria and can be divided into several phylogenetic groups (clusters). There are 228 species and subspecies classified in the genus. Clostridia are large bacteria (3–8 μm long and 0.4–1.2 μm wide) that have the ability to form spores. The germinal forms and their seeds can be distinguished. The germinal form in most Clostridia has the shape of a straight or curved bacterium [1]. Different bacteria attach themselves to solid helical formations.

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