{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T10:13:17Z","timestamp":1790935997692,"version":"4.1.0"},"reference-count":33,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2004,10,27]],"date-time":"2004-10-27T00:00:00Z","timestamp":1098835200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecular Microbiology"],"published-print":{"date-parts":[[2005,1]]},"abstract":"<jats:title>Summary<\/jats:title><jats:p> <jats:italic>Clostridium botulinum<\/jats:italic> and <jats:italic>Clostridium tetani<\/jats:italic>, respectively, produce potent toxins, botulinum neurotoxin (BoNT) and tetanus neurotoxin (TeTx), which are responsible for severe diseases, botulism and tetanus. Neurotoxin synthesis is a regulated process in <jats:italic>Clostridium<\/jats:italic>. The genes <jats:italic>botR\/A<\/jats:italic> in <jats:italic>C. botulinum<\/jats:italic> A and <jats:italic>tetR<\/jats:italic> in <jats:italic>C. tetani<\/jats:italic> positively regulate expression of BoNT\/A and associated non\u2010toxic proteins (ANTPs), as well as TeTx respectively. The <jats:italic>botR\/A<\/jats:italic> gene lies in close vicinity of the two operons which contain <jats:italic>bont\/A<\/jats:italic> and <jats:italic>antps<\/jats:italic> genes in <jats:italic>C. botulinum<\/jats:italic> A, and <jats:italic>tetR<\/jats:italic> immediately precedes the <jats:italic>tetX<\/jats:italic> gene in <jats:italic>C. tetani<\/jats:italic>. We show that BotR\/A and TetR function as specific alternative sigma factors rather than positive regulators based on the following results: (i) BotR\/A and TetR associated with target DNAs only in the presence of the RNA polymerase core enzyme (Core), (ii) BotR\/A and TetR directly bound with the core enzyme, (iii) BotR\/A\u2010Core recognized \u221235 and \u221210 regions of <jats:italic>ntnh\u2010bont\/A<\/jats:italic> promoter and (iv) BotR\/A and TetR triggered <jats:italic>in vitro<\/jats:italic> transcription from the target promoters. In <jats:italic>C. botulinum<\/jats:italic> A, <jats:italic>bont\/A<\/jats:italic> and <jats:italic>antps<\/jats:italic> genes are transcribed as bi\u2010 and tricistronic operons controlled by BotR\/A. BotR\/A and TetR are seemingly related to a new subgroup of the \u03c3<jats:sup>70<\/jats:sup> family that includes TcdR and UviA, which, respectively, regulate production of toxins A and B in <jats:italic>C. difficile<\/jats:italic> and bacteriocin in <jats:italic>C. perfringens<\/jats:italic>. Sequences of \u221235 region are highly conserved in the promoter of target toxin genes in <jats:italic>C. botulinum<\/jats:italic>, <jats:italic>C. tetani<\/jats:italic>, <jats:italic>C. difficile<\/jats:italic> and <jats:italic>C. perfringens<\/jats:italic>. Overall, a common regulation mechanism probably controls toxin gene expression in these four toxigenic clostridial species.<\/jats:p>","DOI":"10.1111\/j.1365-2958.2004.04377.x","type":"journal-article","created":{"date-parts":[[2004,12,21]],"date-time":"2004-12-21T23:51:39Z","timestamp":1103673099000},"page":"235-249","source":"Crossref","is-referenced-by-count":57,"title":["BotR\/A and TetR are alternative RNA polymerase sigma factors controlling the expression of the neurotoxin and associated protein genes in <i>Clostridium botulinum<\/i> type A and <i>Clostridium tetani<\/i>"],"prefix":"10.1111","volume":"55","author":[{"given":"St\u00e9phanie","family":"Raffestin","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bruno","family":"Dupuy","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jean 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