Regulation of Clostridium tetani Neurotoxin Expression by Culture Conditions

Pennings, Jeroen L. A.; Abachin, Éric; Esson, Raphaël; Hodemaekers, Hennie M.; Francotte, Antoine; Claude, Jean‐Baptiste; Vanhee, Céline; Uhlrich, Sylvie; Vandebriel, Rob J.

doi:10.3390/toxins14010031

Cited by 2 publications

(2 citation statements)

References 24 publications

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“…An initial pH of 6.1 seems optimal for TeNT production [84]. In a complex medium, high pH (7.8) downregulates tent [99]. The mechanism of toxin gene regulation by pH is not yet identified.…”

Section: Other Nutritional and Environmental Factorsmentioning

confidence: 99%

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Regulatory Networks Controlling Neurotoxin Synthesis in Clostridium botulinum and Clostridium tetani

Popoff

Brüggemann

2022

Toxins

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Clostridium botulinum and Clostridium tetani are Gram-positive, spore-forming, and anaerobic bacteria that produce the most potent neurotoxins, botulinum toxin (BoNT) and tetanus toxin (TeNT), responsible for flaccid and spastic paralysis, respectively. The main habitat of these toxigenic bacteria is the environment (soil, sediments, cadavers, decayed plants, intestinal content of healthy carrier animals). C. botulinum can grow and produce BoNT in food, leading to food-borne botulism, and in some circumstances, C. botulinum can colonize the intestinal tract and induce infant botulism or adult intestinal toxemia botulism. More rarely, C. botulinum colonizes wounds, whereas tetanus is always a result of wound contamination by C. tetani. The synthesis of neurotoxins is strictly regulated by complex regulatory networks. The highest levels of neurotoxins are produced at the end of the exponential growth and in the early stationary growth phase. Both microorganisms, except C. botulinum E, share an alternative sigma factor, BotR and TetR, respectively, the genes of which are located upstream of the neurotoxin genes. These factors are essential for neurotoxin gene expression. C. botulinum and C. tetani share also a two-component system (TCS) that negatively regulates neurotoxin synthesis, but each microorganism uses additional distinct sets of TCSs. Neurotoxin synthesis is interlocked with the general metabolism, and CodY, a master regulator of metabolism in Gram-positive bacteria, is involved in both clostridial species. The environmental and nutritional factors controlling neurotoxin synthesis are still poorly understood. The transition from amino acid to peptide metabolism seems to be an important factor. Moreover, a small non-coding RNA in C. tetani, and quorum-sensing systems in C. botulinum and possibly in C. tetani, also control toxin synthesis. However, both species use also distinct regulatory pathways; this reflects the adaptation of C. botulinum and C. tetani to different ecological niches.

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Section: Other Nutritional and Environmental Factorsmentioning

confidence: 99%

“…However, a high temperature induces the production of protease(s), which inactivate BoNT/A [33]. TeNT production is usually obtained by C. tetani culture at 33-35 • C [82,84,99].…”

Section: Other Nutritional and Environmental Factorsmentioning

confidence: 99%

Regulatory Networks Controlling Neurotoxin Synthesis in Clostridium botulinum and Clostridium tetani

Popoff

Brüggemann

2022

Toxins

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Expression of Recombinant Clostridial Neurotoxin by C. tetani

Gregg,

Gupta,

Tepp

et al. 2024

Microorganisms

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Tetanus neurotoxins (TeNT) and botulinum neurotoxins (BoNTs) are closely related ~150 kDa protein toxins that together comprise the group of clostridial neurotoxins (CNTs) expressed by various species of Clostridia. While TeNT is expressed as a single polypeptide, BoNTs are always produced alongside multiple non-toxic proteins that form a stabilizing complex with BoNT and are encoded in a conserved toxin gene cluster. It is unknown how tent evolved without a similar gene cluster and why complex-free TeNT is secreted as a stable and soluble protein by C. tetani, whereas complexing proteins appear to be essential for BoNT stability in culture supernatants of C. botulinum. To assess whether the stability of TeNT is due to an innate property of the toxin or is a result of C. tetani’s intra- and extra-cellular environment, both TeNT and complex-free BoNT/A1ERY were expressed recombinantly in atoxic C. tetani and analyzed for expression and stability. The strong clostridial ferredoxin (fdx) promotor resulted in the expression of recombinant TeNT at greater levels and earlier time points than endogenously produced TeNT. Recombinant BoNT/A1ERY was similarly expressed by atoxic C. tetani, although partial degradation was observed. The rBoNT/A1ERY produced in C. tetani was also partially proteolytically processed to the dichain form. Investigations of bacterial growth media and pH conditions found that the stability of rTeNT and rBoNT/A1ERY in spent media of C. tetani or C. botulinum was affected by growth media but not by pH. These data indicate that the distinct metabolism of C. tetani or C. botulinum under various growth conditions is a primary factor in creating a more or less favorable environment for complex-free CNT stability.

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Regulation of Clostridium tetani Neurotoxin Expression by Culture Conditions

Cited by 2 publications

References 24 publications

Regulatory Networks Controlling Neurotoxin Synthesis in Clostridium botulinum and Clostridium tetani

Regulatory Networks Controlling Neurotoxin Synthesis in Clostridium botulinum and Clostridium tetani

Expression of Recombinant Clostridial Neurotoxin by C. tetani

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