Variability of Botulinum Toxins: Challenges and Opportunities for the Future

Self Cite

Human botulism is a severe disease characterized by flaccid paralysis and inhibition of certain gland secretions, notably salivary secretions, caused by inhibition of neurotransmitter release. Naturally acquired botulism occurs in three main forms: food-borne botulism by ingestion of preformed botulinum neurotoxin (BoNT) in food, botulism by intestinal colonization (infant botulism and intestinal toxemia botulism in infants above one year and adults), and wound botulism. A rapid laboratory confirmation of botulism is required for the appropriate management of patients. Detection of BoNT in the patient’s sera is the most direct way to address the diagnosis of botulism. Based on previous published reports, botulinum toxemia was identified in about 70% of food-borne and wound botulism cases, and only in about 28% of infant botulism cases, in which the diagnosis is mainly confirmed from stool sample investigation. The presence of BoNT in serum depends on the BoNT amount ingested with contaminated food or produced locally in the intestine or wound, and the timeframe between serum sampling and disease onset. BoNT levels in patient’s sera are most frequently low, requiring a highly sensitive method of detection. Mouse bioassay is still the most used method of botulism identification from serum samples. However, in vitro methods based on BoNT endopeptidase activity with detection by mass spectrometry or immunoassay have been developed and depending on BoNT type, are more sensitive than the mouse bioassay. These new assays show high specificity for individual BoNT types and allow more accurate differentiation between positive toxin sera from botulism and autoimmune neuropathy patients.

Section: Introductionmentioning

confidence: 99%

“…Toxin detection in patient's sera by mouse bioassay,2 BoNT typing was reported for only 15 serum samples,3 C. baratii producing BoNT/F detected in stool or food,4 Distribution of the botulism types during this period,5 BoNT/B detected in remaining ham,6 BoNT/E detected in remnant salted fish,7 Detection of BoNT types A and B.…”

mentioning

confidence: 99%

Toxemia in Human Naturally Acquired Botulism

Rasetti-Escargueil

Lemichez

Popoff

2020

Self Cite

“…Further description of the mechanism of binding, internalization, and mode of action of the different BoNTs serotypes is beyond the purpose of this review and the reader is strongly encouraged to refer to some excellent reviews present in the literature. For example, see the reviews of Rossetto et al [36], Pirazzini et al [37] or Rasetti-Escargueil et al [38], which cover all the biological, pharmacological, and toxicological aspects related to the use of BoNTs.…”

Section: Botulinum Toxin and Nerve Regeneration After Peripheral Injumentioning

confidence: 99%

Botulinum Toxin and Neuronal Regeneration after Traumatic Injury of Central and Peripheral Nervous System

Luvisetto

2020

Botulinum neurotoxins (BoNTs) are toxins produced by the bacteria Clostridium botulinum, the causing agent for botulism, in different serotypes, seven of which (A–G) are well characterized, while others, such as H or FA, are still debated. BoNTs exert their action by blocking SNARE (soluble N-ethylmale-imide-sensitive factor-attachment protein receptors) complex formation and vesicle release from the neuronal terminal through the specific cleavage of SNARE proteins. The action of BoNTs at the neuromuscular junction has been extensively investigated and knowledge gained in this field has set the foundation for the use of these toxins in a variety of human pathologies characterized by excessive muscle contractions. In parallel, BoNTs became a cosmetic drug due to its power to ward off facial wrinkles following the activity of the mimic muscles. Successively, BoNTs became therapeutic agents that have proven to be successful in the treatment of different neurological disorders, with new indications emerging or being approved each year. In particular, BoNT/A became the treatment of excellence not only for muscle hyperactivity conditions, such as dystonia and spasticity, but also to reduce pain in a series of painful states, such as neuropathic pain, lumbar and myofascial pain, and to treat various dysfunctions of the urinary bladder. This review summarizes recent experimental findings on the potential efficacy of BoNTs in favoring nerve regeneration after traumatic injury in the peripheral nervous system, such as the injury of peripheral nerves, like sciatic nerve, and in the central nervous system, such as spinal cord injury.

“…A double-chain protein with a molecular weight of 150 kDa, it exists in seven different serotypes (A to G) and more than 40 subtypes. In the past few years, using bioinformatics, data mining and high-throughput sequencing techniques, other subtypes of BoNT have been discovered, as well as new BoNT-like toxins produced by members of non-clostridial bacterial species (e.g., Enterococcus faecium and Chryseobacterium piperi) [1,2].…”

Section: Introductionmentioning

confidence: 99%

Biosecurity Threat Posed by Botulinum Toxin

Cenciarelli

Riley

Baka

2019

The deliberate release of biological agents with terrorist or criminal intent continues to pose concerns in the current geopolitical situation. Therefore, attention is still needed to ensure preparedness against the potential use of pathogens as unconventional weapons. Botulinum neurotoxin (BoNT) is one such biological threat, characterized by an extremely low lethal dose, high morbidity and mortality when appropriately disseminated, and the capacity to cause panic and social disruption. This paper addresses the risks of a potential release of the botulinum neurotoxin and summarizes the relevant aspects of the threat.