New targets in the search for preventive and therapeutic agents for botulism

Abstract

Botulism is a severe neuroparalytic disease resulting from exposure to one of the most poisonous toxins to humans. Because of this high potency and the use of toxins as biological weapons, botulism is a public health concern and each case represents an emergency. Current therapy involves respiratory supportive care and anti-toxins administration. As a preventive measure, vaccination against toxins represents an effective strategy but is undesirable due the rarity of botulism and the effectiveness of toxins in treating several neuromuscular disorders. This paper summarizes the current issues in botulism treatment and prevention, highlighting the challenge for future researches.

Keywords::

• bacteriocins
• botulinum toxin
• botulism
• inhibitors
• microbial antagonism
• prevention
• therapy
• vaccine

Acknowledgements

The authors would like to thank Mandarino G for the language revision of the manuscript.

Financial & competing interests disclosure

The authors have no relevant affiliation or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or material discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or option, expert testimony, grants or patents received or pending or royalties.

No writing assistance was utilized in the production of this manuscript.

Key issues

• Botulism is a rare but severe neuroparalytic disease due to exposure to botulinum toxins (BoNTs) that block the release of acetylcholine neurotransmitter from presynaptic neurons into the neuromuscular junctions.

• BoNTs are the most potent poison known to humans. The consumption of little amount of food contaminated with toxin can result in botulism.

• BoNT-producing clostridia are a heterogeneous group of gram-positive, spore-forming, anaerobic bacteria capable of producing BoNTs.

• Currently, the treatment of botulism is based on supportive measures consisting of artificial respiration and passive administration of anti-BoNT immune globulin.

• The most effective means of defending against the toxins is by inducing a protective immune response through vaccination.

• Improving vaccine technology against botulinum toxin plays a crucial role not only in providing active immunity to at-risk population, but also as a prerequisite for the production of immunoglobulins used for passive immunization.

• Anti-toxins neutralize only the circulating toxin molecules still unbound to the nerve endings and cannot reverse the paralysis of botulism.

• Several peptidic and non-peptidic small molecule candidate to become anti-botulinum drugs have been developed on the basis of the cleavage site sequence of the different BoNTs, as well as using phage display technology.

• Aptamers targeting the endopeptidase activity of BoNTs can be used as the therapeutic agents to reverse the clinic syndrome of botulism when combined with a proper delivery system.

• The inhibition of BoNT-producing clostridia spores germination, growth and toxin production represents an effective measure to prevent botulism.