Pathogenicity and virulence of Clostridium botulinum .
Alexander M RawsonAndrew W DempsterChristopher M HumphreysNigel Peter MintonPublished in: Virulence (2023)
Clostridium botulinum , a polyphyletic Gram-positive taxon of bacteria, is classified purely by their ability to produce botulinum neurotoxin (BoNT). BoNT is the primary virulence factor and the causative agent of botulism. A potentially fatal disease, botulism is classically characterized by a symmetrical descending flaccid paralysis, which is left untreated can lead to respiratory failure and death. Botulism cases are classified into three main forms dependent on the nature of intoxication; foodborne, wound and infant. The BoNT, regarded as the most potent biological substance known, is a zinc metalloprotease that specifically cleaves SNARE proteins at neuromuscular junctions, preventing exocytosis of neurotransmitters, leading to muscle paralysis. The BoNT is now used to treat numerous medical conditions caused by overactive or spastic muscles and is extensively used in the cosmetic industry due to its high specificity and the exceedingly small doses needed to exert long-lasting pharmacological effects. Additionally, the ability to form endospores is critical to the pathogenicity of the bacteria. Disease transmission is often facilitated via the metabolically dormant spores that are highly resistant to environment stresses, allowing persistence in the environment in unfavourable conditions. Infant and wound botulism infections are initiated upon germination of the spores into neurotoxin producing vegetative cells, whereas foodborne botulism is attributed to ingestion of preformed BoNT. C. botulinum is a saprophytic bacterium, thought to have evolved its potent neurotoxin to establish a source of nutrients by killing its host.
Keyphrases
- biofilm formation
- respiratory failure
- escherichia coli
- pseudomonas aeruginosa
- staphylococcus aureus
- induced apoptosis
- antimicrobial resistance
- healthcare
- multidrug resistant
- mechanical ventilation
- gram negative
- skeletal muscle
- anti inflammatory
- heavy metals
- cell death
- oxidative stress
- signaling pathway
- candida albicans
- cell proliferation
- cerebral palsy
- cell cycle arrest
- surgical site infection
- endoplasmic reticulum stress
- cystic fibrosis
- single molecule
- structural basis