title: The pattern of growth observed for Clostridium botulinum type A1 strain ATCC 19397 is influenced by nutritional status and quorum sensing: a modelling perspective.
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.
authors.affiliation: Gut Health and Food Safety, Institute of Food Research, Norwich Research Park, Colney, Norwich NR4 7UA, UK adaoha.ihekwaba@ifr.ac.uk.
authors.forename: Adaoha E C
authors.initials: AE
authors.lastname: Ihekwaba
authors.affiliation: Faculty of Engineering, EAN University, Carrera 11 No. 78 - 47, Bogotá, Colombia.
authors.forename: Ivan
authors.initials: I
authors.lastname: Mura
authors.affiliation: Gut Health and Food Safety, Institute of Food Research, Norwich Research Park, Colney, Norwich NR4 7UA, UK.
authors.forename: Michael W
authors.initials: MW
authors.lastname: Peck
authors.affiliation: Gut Health and Food Safety, Institute of Food Research, Norwich Research Park, Colney, Norwich NR4 7UA, UK.
authors.forename: G C
authors.initials: GC
authors.lastname: Barker
mesh_terms: D000693:Anaerobiosis; D000818:Animals; D019274:Botulinum Toxins, Type A / Q000096:biosynthesis; D047013:Clostridium botulinum type A / Q000254:growth & development* / Q000378:metabolism* / Q000502:physiology; D003470:Culture Media / Q000737:chemistry; D006801:Humans; D008962:Models, Theoretical; D053038:Quorum Sensing
chemical_list: D003470:Culture Media; D019274:Botulinum Toxins, Type A
keywords: C. botulinum; bacterial growth; mathematical modelling; nutrient sensitivity; population dynamics; quorum sensing; toxin regulation