Evidence map›Paper›PMID 35110559›Full record

ArticleScientific reports2022

Construction and validation of safe Clostridium botulinum Group II surrogate strain producing inactive botulinum neurotoxin type E toxoid.

Maria B Nowakowska, Katja Selby, Adina Przykopanski, Maren Krüger, Nadja Krez, Brigitte G Dorner, Martin B Dorner, Rongsheng Jin, Nigel P Minton, Andreas Rummel and 1 more

Abstract read
In one paragraph

Article in Scientific reports, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.

0numbers the graph read from it
0cells of the map it votes in
9citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

9 citing papers in PubMed.

  1. Article
  2. Article
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  4. Review
  5. Review
  6. Specific Isolation ofInternational journal of molecular sciences · 2022
    Article
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  8. Review
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

11 authors.

Maria B NowakowskaDepartment of Food Hygiene and Environmental Health, Faculty of Veterinary Medicine, University of Helsinki, Helsinki, Finland.
Katja SelbyDepartment of Food Hygiene and Environmental Health, Faculty of Veterinary Medicine, University of Helsinki, Helsinki, Finland.
Adina PrzykopanskiInstitut Für Toxikologie, Medizinische Hochschule Hannover, Hannover, Germany.
Maren KrügerBiological Toxins, Centre for Biological Threats and Special Pathogens, Robert Koch Institute, Berlin, Germany.
Nadja KrezInstitut Für Toxikologie, Medizinische Hochschule Hannover, Hannover, Germany.
Brigitte G DornerBiological Toxins, Centre for Biological Threats and Special Pathogens, Robert Koch Institute, Berlin, Germany.
Martin B DornerBiological Toxins, Centre for Biological Threats and Special Pathogens, Robert Koch Institute, Berlin, Germany.
Rongsheng JinDepartment of Physiology and Biophysics, University of California, Irvine, CA, USA.
Nigel P MintonClostridia Research Group, BBSRC/EPSRC Synthetic Biology Research Centre (SBRC), School of Life Sciences, Biodiscovery Institute, University of Nottingham, Nottingham, UK.
Andreas RummelInstitut Für Toxikologie, Medizinische Hochschule Hannover, Hannover, Germany.
Miia LindströmDepartment of Food Hygiene and Environmental Health, Faculty of Veterinary Medicine, University of Helsinki, Helsinki, Finland. miia.lindstrom@helsinki.fi.

Funding

Molecular mechanisms of botulinum neurotoxin neutralizationR01AI125704 · NIAID · UNIVERSITY OF CALIFORNIA-IRVINE · PI JIN, RONGSHENG, SHOEMAKER, CHARLES BIX · 2016 to 2020
$3.0M
NIAID NIH HHS R01 AI125704
6 · The paper itself

Abstract

Botulinum neurotoxins (BoNTs), produced by the spore-forming bacterium Clostridium botulinum, cause botulism, a rare but fatal illness affecting humans and animals. Despite causing a life-threatening disease, BoNT is a multipurpose therapeutic. Nevertheless, as the most potent natural toxin, BoNT is classified as a Select Agent in the US, placing C. botulinum research under stringent governmental regulations. The extreme toxicity of BoNT, its impact on public safety, and its diverse therapeutic applications urge to devise safe solutions to expand C. botulinum research. Accordingly, we exploited CRISPR/Cas9-mediated genome editing to introduce inactivating point mutations into chromosomal bont/e gene of C. botulinum Beluga E. The resulting Beluga Ei strain displays unchanged physiology and produces inactive BoNT (BoNT/Ei) recognized in serological assays, but lacking biological activity detectable ex- and in vivo. Neither native single-chain, nor trypsinized di-chain form of BoNT/Ei show in vivo toxicity, even if isolated from Beluga Ei sub-cultured for 25 generations. Beluga Ei strain constitutes a safe alternative for the BoNT research necessary for public health risk management, the development of food preservation strategies, understanding toxinogenesis, and for structural BoNT studies. The example of Beluga Ei generation serves as template for future development of C. botulinum producing different inactive BoNT serotypes.

Indexed as

CRISPR-Cas SystemsGene EditingBotulinum ToxinsClostridium botulinumClustered Regularly Interspaced Short Palindromic RepeatsCRISPR-Associated Protein 9GenotypePhenotypePoint MutationBotulinum Toxinsbotulinum toxin type ECRISPR-Associated Protein 9

Identifiers

PMID35110559
PMCPMC8810926

What OpenQuestion holds

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.