Neurotoxin synthesis is positively regulated by the sporulation transcription factor Spo0A in Clostridium botulinum type E
Summary Clostridium botulinum produces the most potent natural toxin, the botulinum neurotoxin (BoNT), probably to create anaerobiosis and nutrients by killing the host, and forms endospores that facilitate survival in harsh conditions and transmission. Peak BoNT production coincides with initiation...
Published in: | Environmental Microbiology |
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crwiley:10.1111/1462-2920.13892 2024-09-09T19:33:20+00:00 Neurotoxin synthesis is positively regulated by the sporulation transcription factor Spo0A in Clostridium botulinum type E Mascher, Gerald Mertaoja, Anna Korkeala, Hannu Lindström, Miia European Research Council Suomen Akatemia Finnish Foundation of Veterinary Research 2017 http://dx.doi.org/10.1111/1462-2920.13892 https://api.wiley.com/onlinelibrary/tdm/v1/articles/10.1111%2F1462-2920.13892 http://onlinelibrary.wiley.com/wol1/doi/10.1111/1462-2920.13892/fullpdf en eng Wiley http://onlinelibrary.wiley.com/termsAndConditions#vor Environmental Microbiology volume 19, issue 10, page 4287-4300 ISSN 1462-2912 1462-2920 journal-article 2017 crwiley https://doi.org/10.1111/1462-2920.13892 2024-08-01T04:23:01Z Summary Clostridium botulinum produces the most potent natural toxin, the botulinum neurotoxin (BoNT), probably to create anaerobiosis and nutrients by killing the host, and forms endospores that facilitate survival in harsh conditions and transmission. Peak BoNT production coincides with initiation of sporulation in C . botulinum cultures, which suggests common regulation. Here, we show that Spo0A, the master regulator of sporulation, positively regulates BoNT production. Insertional inactivation of spo0A in C . botulinum type E strain Beluga resulted in significantly reduced BoNT production and in abolished or highly reduced sporulation in relation to wild‐type controls. Complementation with spo0A restored BoNT production and sporulation. Recombinant DNA‐binding domain of Spo0A directly bound to a putative Spo0A‐binding box (CTTCGAA) within the BoNT/E operon promoter, demonstrating direct regulation. Spo0A is the first neurotoxin regulator reported in C . botulinum type E. Unlike other C . botulinum strains that are terrestrial and employ the alternative sigma factor BotR in directing BoNT expression, C . botulinum type E strains are adapted to aquatic ecosystems, possess distinct epidemiology and lack BotR. Our results provide fundamental new knowledge on the genetic control of BoNT production and demonstrate common regulation of BoNT production and sporulation, providing a key intervention point for control. Article in Journal/Newspaper Beluga Beluga* Wiley Online Library Environmental Microbiology 19 10 4287 4300 |
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Wiley Online Library |
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English |
description |
Summary Clostridium botulinum produces the most potent natural toxin, the botulinum neurotoxin (BoNT), probably to create anaerobiosis and nutrients by killing the host, and forms endospores that facilitate survival in harsh conditions and transmission. Peak BoNT production coincides with initiation of sporulation in C . botulinum cultures, which suggests common regulation. Here, we show that Spo0A, the master regulator of sporulation, positively regulates BoNT production. Insertional inactivation of spo0A in C . botulinum type E strain Beluga resulted in significantly reduced BoNT production and in abolished or highly reduced sporulation in relation to wild‐type controls. Complementation with spo0A restored BoNT production and sporulation. Recombinant DNA‐binding domain of Spo0A directly bound to a putative Spo0A‐binding box (CTTCGAA) within the BoNT/E operon promoter, demonstrating direct regulation. Spo0A is the first neurotoxin regulator reported in C . botulinum type E. Unlike other C . botulinum strains that are terrestrial and employ the alternative sigma factor BotR in directing BoNT expression, C . botulinum type E strains are adapted to aquatic ecosystems, possess distinct epidemiology and lack BotR. Our results provide fundamental new knowledge on the genetic control of BoNT production and demonstrate common regulation of BoNT production and sporulation, providing a key intervention point for control. |
author2 |
European Research Council Suomen Akatemia Finnish Foundation of Veterinary Research |
format |
Article in Journal/Newspaper |
author |
Mascher, Gerald Mertaoja, Anna Korkeala, Hannu Lindström, Miia |
spellingShingle |
Mascher, Gerald Mertaoja, Anna Korkeala, Hannu Lindström, Miia Neurotoxin synthesis is positively regulated by the sporulation transcription factor Spo0A in Clostridium botulinum type E |
author_facet |
Mascher, Gerald Mertaoja, Anna Korkeala, Hannu Lindström, Miia |
author_sort |
Mascher, Gerald |
title |
Neurotoxin synthesis is positively regulated by the sporulation transcription factor Spo0A in Clostridium botulinum type E |
title_short |
Neurotoxin synthesis is positively regulated by the sporulation transcription factor Spo0A in Clostridium botulinum type E |
title_full |
Neurotoxin synthesis is positively regulated by the sporulation transcription factor Spo0A in Clostridium botulinum type E |
title_fullStr |
Neurotoxin synthesis is positively regulated by the sporulation transcription factor Spo0A in Clostridium botulinum type E |
title_full_unstemmed |
Neurotoxin synthesis is positively regulated by the sporulation transcription factor Spo0A in Clostridium botulinum type E |
title_sort |
neurotoxin synthesis is positively regulated by the sporulation transcription factor spo0a in clostridium botulinum type e |
publisher |
Wiley |
publishDate |
2017 |
url |
http://dx.doi.org/10.1111/1462-2920.13892 https://api.wiley.com/onlinelibrary/tdm/v1/articles/10.1111%2F1462-2920.13892 http://onlinelibrary.wiley.com/wol1/doi/10.1111/1462-2920.13892/fullpdf |
genre |
Beluga Beluga* |
genre_facet |
Beluga Beluga* |
op_source |
Environmental Microbiology volume 19, issue 10, page 4287-4300 ISSN 1462-2912 1462-2920 |
op_rights |
http://onlinelibrary.wiley.com/termsAndConditions#vor |
op_doi |
https://doi.org/10.1111/1462-2920.13892 |
container_title |
Environmental Microbiology |
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19 |
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10 |
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4287 |
op_container_end_page |
4300 |
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1809902718228103168 |