Bacterial toxins cause severe illnesses in both humans and animals, with conditions such as necrotic enteritis, gas gangrene, and tetraplegia. While toxin production may offer bacteria an advantage in adverse ecological niches, it likely comes at a cost to their overall fitness. Bacterial populations likely regulate toxin production based on metabolic needs, with non-competitive environments favouring phenotypes that minimize toxin production. Understanding the genetic and cellular mechanisms bacteria employ to modulate toxin production in response to their environment is crucial for developing interventions aimed at disease prevention, antitoxin and vaccine development, and preservation of foods and feeds. Specifically, botulism is caused by botulinum neurotoxins (BOT) from Clostridium botulinum and is a potentially life-threatening disease that results in paralysis and respiratory failure. C. botulinum may thrive and produce BOT in various environments, including foods, dysbiotic gut, deep wounds and abscesses, and decaying matter. Interestingly, BOT is also widely used for medical indications, further justifying the need to characterize C. botulinum and BOT production. In C. botulinum cells, BOT production is linked to metabolic processes and sporulation. Understanding the relationship between these processes could help developing prophylactic and control measures and better understanding the epidemiology of different forms of human botulism. whyBOTher articulated around four main questions: how C. botulinum cultures coordinate BOT production and related traits among single cells and populations in response to their environment, which cellular regulatory and metabolic systems C. botulinum uses to control BOT production, which DNA-related alterations C. botulinum makes to control or give up BOT production, and how BOT works.
