Abstract
Botulinum neurotoxins (BoNTs) produced by the anaerobic bacterium Clostridium botulinum are the most poisonous substances known to mankind. However, toxin regulation and signals triggering synthesis as well as the regulatory network and actors controlling toxin production are unknown. Experiments show that the neurotoxin gene is growth phase dependent for C. botulinum type A1 strain ATCC 19397, and toxin production is influenced both by culture conditions and nutritional status of the medium. Building mathematical models to describe the genetic and molecular machinery that drives the synthesis and release of BoNT requires a simultaneous description of the growth of the bacterium in culture. Here, we show four plausible modelling options which could be considered when constructing models describing the pattern of growth observed in a botulinum growth medium. Commonly used bacterial growth models are unsuitable to fit the pattern of growth observed, since they only include monotonic growth behaviour. We find that a model that includes both the nutritional status and the ability of the cells to sense their surroundings in a quorum-sensing manner is most successful at explaining the pattern of growth obtained for C. botulinum type A1 strain ATCC 19397.
Highlights
Clostridium botulinum is a Gram-positive obligately anaerobic, endospore-forming bacterium that produces a lethal neurotoxin called botulinum neurotoxin (BoNT) (Schantz and Johnson 1992; Peck 2009)
Since bont gene expression is growth phase dependent and the concentration of toxin released in the botulinum growth medium is related to the number of bacterial cells, creating a comprehensive computational model of Botulinum neurotoxins (BoNTs) production required growth data expressed in terms of microbial number (i.e. reported as viable cell counts)
We present a set of modelling options: four different physiological bases that could account for the observed dynamics of the C. botulinum population in the selected strain ATCC 19397 experimental data set
Summary
Clostridium botulinum is a Gram-positive obligately anaerobic, endospore-forming bacterium that produces a lethal neurotoxin called botulinum neurotoxin (BoNT) (Schantz and Johnson 1992; Peck 2009). BoNTs, highly potent substances with an estimated human lethal dose of ∼30–100 ng (Schantz and Johnson 1992; Peck 2009), are the most powerful toxins known affecting human and animal health. What is known is that the bont gene expression appears to be tightly regulated through positive regulatory elements, including the participation of BotR (Marvaud et al 1998), CLC 1093/CLC 1094, CLC 1914/CLC 1913 and CLC 0661/CLC 0663 two-component signal transduction systems (Connan et al 2012), CodY (Zhang et al 2014) and an Agr quorum-sensing system (Cooksley et al 2010). The quantity of BoNT produced is strain dependent and influenced by culture conditions including the nutritional status of the medium (e.g. nitrogen sources), but the precise mechanisms are unknown
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
