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...

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Bibliographic Details
Published in:Environmental Microbiology
Main Authors: Mascher, Gerald, Mertaoja, Anna, Korkeala, Hannu, Lindström, Miia
Other Authors: European Research Council, Suomen Akatemia, Finnish Foundation of Veterinary Research
Format: Article in Journal/Newspaper
Language:English
Published: Wiley 2017
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Online Access: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
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Summary: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.