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Neurotoxin synthesis is positively regulated by the sporulation transcription factor Spo0A in Clostridium botulinum type E
Author(s) -
Mascher Gerald,
Mertaoja Anna,
Korkeala Hannu,
Lindström Miia
Publication year - 2017
Publication title -
environmental microbiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.954
H-Index - 188
eISSN - 1462-2920
pISSN - 1462-2912
DOI - 10.1111/1462-2920.13892
Subject(s) - biology , clostridium botulinum , microbiology and biotechnology , sigma factor , operon , regulator , neurotoxin , complementation , toxin , genetics , gene , mutant , promoter , biochemistry , gene expression
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.