ArticlePLoS pathogens2013
Two-component signal transduction system CBO0787/CBO0786 represses transcription from botulinum neurotoxin promoters in Clostridium botulinum ATCC 3502.
Article in PLoS pathogens, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 37 citations in OpenAlex.
- Pathogenicity and virulence ofVirulence · 2023Review
- Specific Isolation ofInternational journal of molecular sciences · 2022Article
- Review
- Posttranslational Regulation of Botulinum Neurotoxin Production in Clostridium botulinum Hall A-mSphere · 2021Article
- Phage lysin that specifically eliminates Clostridium botulinum Group I cells.Scientific reports · 2020Article
- Tetanus Toxin Synthesis is Under the Control of A Complex Network of Regulatory Genes inToxins · 2020Article
- Review
- Clostridial Genetics: Genetic Manipulation of the Pathogenic Clostridia.Microbiology spectrum · 2019Review
- Regulation of Botulinum Neurotoxin Synthesis and Toxin Complex Formation by Arginine and Glucose in Clostridium botulinum ATCC 3502.Applied and environmental microbiology · 2017Article
- Article
- An Integrative Approach to Computational Modelling of the Gene Regulatory Network Controlling Clostridium botulinum Type A1 Toxin Production.PLoS computational biology · 2016Article
- SBRC-Nottingham: sustainable routes to platform chemicals from C1 waste gases.Biochemical Society transactions · 2016Article
- New Elements To Consider When Modeling the Hazards Associated with Botulinum Neurotoxin in Food.Journal of bacteriology · 2016Review
- The pattern of growth observed for Clostridium botulinum type A1 strain ATCC 19397 is influenced by nutritional status and quorum sensing: a modelling perspective.Pathogens and disease · 2015Article
- Virulence Plasmids of Spore-Forming Bacteria.Microbiology spectrum · 2014Review
- Positive regulation of botulinum neurotoxin gene expression by CodY in Clostridium botulinum ATCC 3502.Applied and environmental microbiology · 2014Article
- Biotechnological applications of mobile group II introns and their reverse transcriptases: gene targeting, RNA-seq, and non-coding RNA analysis.Mobile DNA · 2014Article
- The cold-induced two-component system CBO0366/CBO0365 regulates metabolic pathways with novel roles in group I Clostridium botulinum ATCC 3502 cold tolerance.Applied and environmental microbiology · 2014Article
- Transcriptomic analysis of (group I) Clostridium botulinum ATCC 3502 cold shock response.PloS one · 2014Article
- The CLO3403/CLO3404 two-component system of Clostridium botulinum E1 Beluga is important for cold shock response and growth at low temperatures.Applied and environmental microbiology · 2014Article
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 2 countries.
Funding
Abstract
Blocking neurotransmission, botulinum neurotoxin is the most poisonous biological substance known to mankind. Despite its infamy as the scourge of the food industry, the neurotoxin is increasingly used as a pharmaceutical to treat an expanding range of muscle disorders. Whilst neurotoxin expression by the spore-forming bacterium Clostridium botulinum appears tightly regulated, to date only positive regulatory elements, such as the alternative sigma factor BotR, have been implicated in this control. The identification of negative regulators has proven to be elusive. Here, we show that the two-component signal transduction system CBO0787/CBO0786 negatively regulates botulinum neurotoxin expression. Single insertional inactivation of cbo0787 encoding a sensor histidine kinase, or of cbo0786 encoding a response regulator, resulted in significantly elevated neurotoxin gene expression levels and increased neurotoxin production. Recombinant CBO0786 regulator was shown to bind to the conserved -10 site of the core promoters of the ha and ntnh-botA operons, which encode the toxin structural and accessory proteins. Increasing concentration of CBO0786 inhibited BotR-directed transcription from the ha and ntnh-botA promoters, demonstrating direct transcriptional repression of the ha and ntnh-botA operons by CBO0786. Thus, we propose that CBO0786 represses neurotoxin gene expression by blocking BotR-directed transcription from the neurotoxin promoters. This is the first evidence of a negative regulator controlling botulinum neurotoxin production. Understanding the neurotoxin regulatory mechanisms is a major target of the food and pharmaceutical industries alike.
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Registered trials
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.