Tetanus Toxin Synthesis is Under the Control of A Complex Network of Regulatory Genes in Clostridium tetani
| Autor: | Lucile Plourde, Vincent Colombié, Olivier Gorgette, Dominique Garnier, Cecile Deneve, Diana Chapeton-Montes, Christine Schmitt, Holger Brüggemann, Catherine Thouvenot, Fabien Barbirato, Sandy Demay, Michel R. Popoff, Georges Michel Haustant |
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| Přispěvatelé: | Bactéries anaérobies et Toxines, Institut Pasteur [Paris], Sanofi Pasteur [Marcy-l'Étoile, France], Plateforme BioImagerie Ultrastructurale – Ultrastructural BioImaging Platform (UTechS UBI), Aarhus University [Aarhus], This research was funded by grant from Sanofi-Pasteur, Marcy l’Etoile and by Institut Pasteur, Paris., Institut Pasteur [Paris] (IP) |
| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
Clostridium tetani
Operon Health Toxicology and Mutagenesis lcsh:Medicine Toxicology medicine.disease_cause POSITIVE REGULATOR INORGANIC-PHOSPHATE chemistry.chemical_compound CARBON-DIOXIDE MESH: Clostridium tetani Sigma factor Clostridium botulinum MESH: Bacterial Proteins Regulator gene MESH: Gene Regulatory Networks CLOSTRIDIUM-BOTULINUM 0303 health sciences MESH: Gene Expression Regulation Bacterial GENOME SEQUENCE FACTOR SPO0A MESH: Carbonates Tetanus toxin MESH: Phosphates tetanus toxin EXPRESSION MESH: Trans-Activators [SDV.BC]Life Sciences [q-bio]/Cellular Biology Biology PROTEIN GENES Microbiology 03 medical and health sciences Two-component system MESH: Promoter Regions Genetic medicine TetR MESH: Tetanus Toxin Gene 030304 developmental biology 030306 microbiology MESH: Transcription Genetic lcsh:R Promoter gene transcription body regions chemistry two-component system NEUROTOXIN VIRULENCE |
| Zdroj: | Chapeton-Montes, D, Plourde, L, Deneve, C, Garnier, D, Barbirato, F, Colombié, V, Demay, S, Haustant, G, Gorgette, O, Schmitt, C, Thouvenot, C, Brüggemann, H & Popoff, M R 2020, ' Tetanus Toxin Synthesis is Under the Control of A Complex Network of Regulatory Genes in Clostridium tetani ', Toxins, vol. 12, no. 5, 328 . https://doi.org/10.3390/toxins12050328 Toxins Toxins, MDPI, 2020, 12 (5), pp.328. ⟨10.3390/toxins12050328⟩ Volume 12 Issue 5 Toxins, Vol 12, Iss 328, p 328 (2020) Toxins, 2020, 12 (5), pp.328. ⟨10.3390/toxins12050328⟩ |
| ISSN: | 2072-6651 |
| Popis: | Clostridium tetani produces a potent neurotoxin, the tetanus toxin (TeNT), which is responsible for an often-fatal neurological disease (tetanus) characterized by spastic paralysis. Prevention is efficiently acquired by vaccination with the TeNT toxoid, which is obtained by C. tetani fermentation and subsequent purification and chemical inactivation. C. tetani synthesizes TeNT in a regulated manner. Indeed, the TeNT gene (tent) is mainly expressed in the late exponential and early stationary growth phases. The gene tetR (tetanus regulatory gene), located immediately upstream of tent, encodes an alternative sigma factor which was previously identified as a positive regulator of tent. In addition, the genome of C. tetani encodes more than 127 putative regulators, including 30 two-component systems (TCSs). Here, we investigated the impact of 12 regulators on TeNT synthesis which were selected based on their homology with related regulatory elements involved in toxin production in other clostridial species. Among nine TCSs tested, three of them impact TeNT production, including two positive regulators that indirectly stimulate tent and tetR transcription. One negative regulator was identified that interacts with both tent and tetR promoters. Two other TCSs showed a moderate effect: one binds to the tent promoter and weakly increases the extracellular TeNT level, and another one has a weak inverse effect. In addition, CodY (control of dciA (decoyinine induced operon) Y) but not Spo0A (sporulation stage 0) or the DNA repair protein Mfd (mutation frequency decline) positively controls TeNT synthesis by interacting with the tent promoter. Moreover, we found that inorganic phosphate and carbonate are among the environmental factors that control TeNT production. Our data show that TeNT synthesis is under the control of a complex network of regulators that are largely distinct from those involved in the control of toxin production in Clostridium botulinum or Clostridium difficile. |
| Databáze: | OpenAIRE |
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