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| [PMID]: | 28455330 |
| [Au] Autor: | Fredrick CM; Lin G; Johnson EA |
| [Ad] Endereço: | Department of Bacteriology, University of Wisconsin-Madison, Madison, Wisconsin, USA. |
| [Ti] Título: | Regulation of Botulinum Neurotoxin Synthesis and Toxin Complex Formation by Arginine and Glucose in Clostridium botulinum ATCC 3502. |
| [So] Source: | Appl Environ Microbiol;83(13), 2017 Jul 01. | | [Is] ISSN: | 1098-5336 |
| [Cp] País de publicação: | United States |
| [La] Idioma: | eng |
| [Ab] Resumo: | Botulinum neurotoxin (BoNT), produced by neurotoxigenic clostridia, is the most potent biological toxin known and the causative agent of the paralytic disease botulism. The nutritional, environmental, and genetic regulation of BoNT synthesis, activation, stability, and toxin complex (TC) formation is not well studied. Previous studies indicated that growth and BoNT formation were affected by arginine and glucose in types A and B. In the present study, ATCC 3502 was grown in toxin production medium (TPM) with different levels of arginine and glucose and of three products of arginine metabolism, citrulline, proline, and ornithine. Cultures were analyzed for growth (optical density at 600 nm [OD ]), spore formation, and BoNT and TC formation by Western blotting and immunoprecipitation and for BoNT activity by mouse bioassay. A high level of arginine (20 g/liter) repressed BoNT production approximately 1,000-fold, enhanced growth, slowed lysis, and reduced endospore production by greater than 1,000-fold. Similar effects on toxin production were seen with equivalent levels of citrulline but not ornithine or proline. In TPM lacking glucose, levels of formation of BoNT/A1 and TC were significantly decreased, and extracellular BoNT and TC proteins were partially inactivated after the first day of culture. An understanding of the regulation of growth and BoNT and TC formation should be valuable in defining requirements for BoNT formation in foods and clinical samples, improving the quality of BoNT for pharmaceutical preparations, and elucidating the biological functions of BoNTs for the bacterium. Botulinum neurotoxin (BoNT) is a major food safety and bioterrorism concern and is also an important pharmaceutical, and yet the regulation of its synthesis, activation, and stability in culture media, foods, and clinical samples is not well understood. This paper provides insights into the effects of critical nutrients on growth, lysis, spore formation, BoNT and TC production, and stability of BoNTs of We show that for ATCC 3502 cultured in a complex medium, a high level of arginine repressed BoNT expression by ca. 1,000-fold and also strongly reduced sporulation. Arginine stimulated growth and compensated for a lack of glucose. BoNT and toxin complex proteins were partially inactivated in a complex medium lacking glucose. This work should aid in optimizing BoNT production for pharmaceutical uses, and furthermore, an understanding of the nutritional regulation of growth and BoNT formation may provide insights into growth and BoNT formation in foods and clinical samples and into the enigmatic function of BoNTs in nature. |
| [Mh] Termos MeSH primário: |
Arginina/metabolismo
Toxinas Botulínicas/biossíntese
Botulismo/microbiologia
Clostridium botulinum/genética
Regulação Bacteriana da Expressão Gênica
Glucose/metabolismo
Neurotoxinas/biossíntese
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| [Mh] Termos MeSH secundário: |
Proteínas de Bactérias/genética
Proteínas de Bactérias/metabolismo
Toxinas Botulínicas/genética
Clostridium botulinum/crescimento & desenvolvimento
Clostridium botulinum/metabolismo
Seres Humanos
Neurotoxinas/genética
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| [Pt] Tipo de publicação: | JOURNAL ARTICLE |
[Nm] Nome de substância:
| 0 (Bacterial Proteins); 0 (Neurotoxins); 94ZLA3W45F (Arginine); EC 3.4.24.69 (Botulinum Toxins); IY9XDZ35W2 (Glucose) |
| [Em] Mês de entrada: | 1712 |
| [Cu] Atualização por classe: | 171225 |
[Lr] Data última revisão:
| 171225 |
| [Sb] Subgrupo de revista: | IM |
| [Da] Data de entrada para processamento: | 170430 |
| [St] Status: | MEDLINE |
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