ArticleApplied and environmental microbiology2014
Holotoxin Activity of Botulinum Neurotoxin Subtype A4 Originating from a Nontoxigenic Clostridium botulinum Expression System.
Article in Applied and environmental microbiology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers, 1 of them a synthesis that pooled it.
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Who cites it
18 citing papers in PubMed, 1 synthesis or guideline pooled it, 21 citations in OpenAlex.
- Guideline
- Expression of Recombinant Clostridial Neurotoxin byMicroorganisms · 2024Article
- Potency Evaluations of Recombinant Botulinum Neurotoxin A1 Mutants Designed to Reduce Toxicity.International journal of molecular sciences · 2024Article
- Article
- Recent Developments in Vaccine Design: From Live Vaccines to Recombinant Toxin Vaccines.Toxins · 2023Review
- Botulinum Neurotoxin A4 Has a 1000-Fold Reduced Potency Due to Three Single Amino Acid Alterations in the Protein Receptor Binding Domain.International journal of molecular sciences · 2023Article
- Resolution of Two Steps in Botulinum Neurotoxin Serotype A1 Light Chain Localization to the Intracellular Plasma Membrane.International journal of molecular sciences · 2021Article
- Novel Native and Engineered Botulinum Neurotoxins.Handbook of experimental pharmacology · 2021Review
- Comparative functional analysis of mice after local injection with botulinum neurotoxin A1, A2, A6, and B1 by catwalk analysis.Toxicon : official journal of the International Society on Toxinology · 2019Article
- Engineering Botulinum Toxins to Improve and Expand Targeting and SNARE Cleavage Activity.Toxins · 2018Review
- Substrate cleavage and duration of action of botulinum neurotoxin type FA ("H, HA").Toxicon : official journal of the International Society on Toxinology · 2018Article
- Article
- Botulinum neurotoxin-encoding plasmids can be conjugatively transferred to diverse clostridial strains.Scientific reports · 2018Article
- In vivo onset and duration of action varies for botulinum neurotoxin A subtypes 1-5.Toxicon : official journal of the International Society on Toxinology · 2015Article
- Current status and future directions of botulinum neurotoxins for targeting pain processing.Toxins · 2015Review
- Immunoprecipitation of native botulinum neurotoxin complexes from Clostridium botulinum subtype A strains.Applied and environmental microbiology · 2015Article
- Botulinum Neurotoxin Subtype A4 Originating from Nontoxigenic Clostridium botulinum.Applied and environmental microbiology · 2014Article
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5 authors at 1 institution in 1 country.
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Abstract
Clostridium botulinum subtype A4 neurotoxin (BoNT/A4) is naturally expressed in the dual-toxin-producing C. botulinum strain 657Ba at 100× lower titers than BoNT/B. In this study, we describe purification of recombinant BoNT/A4 (rBoNT/A4) expressed in a nonsporulating and nontoxigenic C. botulinum expression host strain. The rBoNT/A4 copurified with nontoxic toxin complex components provided in trans by the expression host and was proteolytically cleaved to the active dichain form. Activity of the recombinant BoNT/A4 in mice and in human neuronal cells was about 1,000-fold lower than that of BoNT/A1, and the recombinant BoNT/A4 was effectively neutralized by botulism heptavalent antitoxin. A previous report using recombinant truncated BoNT/A4 light chain (LC) expressed in Escherichia coli has indicated reduced stability and activity of BoNT/A4 LC compared to BoNT/A1 LC, which was surmounted by introduction of a single-amino-acid substitution, I264R. In order to determine whether this mutation would also affect the holotoxin activity of BoNT/A4, a recombinant full-length BoNT/A4 carrying this mutation as well as a second mutation predicted to increase solubility (L260F) was produced in the clostridial expression system. Comparative analyses of the in vitro, cellular, and in vivo activities of rBoNT/A4 and rBoNT/A4-L260F I264R showed 1,000-fold-lower activity than BoNT/A1 in both the mutated and nonmutated BoNT/A4. This indicates that these mutations do not alter the activity of BoNT/A4 holotoxin. In summary, a recombinant BoNT from a dual-toxin-producing strain was expressed and purified in an endogenous clostridial expression system, allowing analysis of this toxin.
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